Molecular & Biochemical Parasitology 114 (2001) 143– 150

www.parasitology-online.com.

Review
The mucin-like glycoprotein super-family of Trypanosoma cruzi:
structure and biological roles
Alvaro Acosta-Serrano a,*,1, Igor C. Almeida b, Lucio H. Freitas-Junior c,
Nobuko Yoshida c, Sergio Schenkman c
a
Department of Biological Chemistry, Johns Hopkins Uni6ersity School of Medicine, Baltimore, MD 21205, USA
b
Departamento de Parasitologia, ICB2, USP, São Paulo, S.P. 05508 -900, Brazil
c
Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina-UNIFESP, São Paulo, S.P. 04023 -062, Brazil
Received 30 July 2000; accepted 15 September 2000

Abstract

Trypanosoma cruzi expresses at its surface large amounts of mucin-like glycoproteins. The T. cruzi mucins (TcMUC), a group
of highly glycosylated GPI-anchored proteins rich in Thr, Ser, and Pro residues, are expressed in high copy numbers in both insect
and mammalian stages of the parasite. These molecules are encoded by a multigene family and contain a unique type of
glycosylation consisting of several sialylated O-glycans linked to the protein backbone via N-acetylglucosamine residues. The
TcMUC are important because of their role in host cell invasion and the ability to induce secretion of proinflammatory cytokines
and nitric oxide in activated macrophages. The TcMUC are also significant in being the major substrate for the cell surface
trans-sialidase. In this review, we summarize the recent knowledge on the molecular structure and function of this family of T.
cruzi glycoproteins. © 2001 Elsevier Science B.V. All rights reserved.

Keywords: Trypanosoma cruzi; Mucins; Sialic acid; trans-Sialidase; GPI; Glycosylation

1. Introduction drate by weight) polyanionic molecules that are rich in

The surface of the different stages of Trypanosoma
cruzi, the agent of American trypanosomiasis (Chagas’
disease), is covered by a thick coat of glycoconjugates.
The major component of this coat has been identified
as a family of mucin-like glycoproteins. These glyco-
conjugates are highly glycosylated (about 60% carbohy-
Abbre6iations: Gal, galactose; GIPL, glycoinositolphospholipid;
GlcNAc, N-acetylglucosamine; GPI, glycosylphosphatidylinositol; PI,
phosphatidylinositol; LPPG, lipopeptidophosphoglycan; SA, sialic
acid; TcMUC, Trypanosoma cruzi mucins; TS, trans-sialidase.
* Corresponding author. Present address: School of Life Science,
Wellcome Trust Biocentre, Division of Molecular Microbiology and
Biological Chemistry, University of Dundee, Dundee DD1 5EH, UK.
Tel.: + 44-1382-345852; fax: + 44-1382-345764.
E-mail address: a.f.acostaserrano@dundee.ac.uk (A. Acosta-Ser-
rano).
1
Present address: Unite de Biologie des Interactions, Hote-Parasite
Institut Pasteur, 75724 Paris Cedex 15, France.
Thr, Ser and Pro residues (but contain few hydrophobic
amino acids), and are anchored to the plasma mem-
brane via a glycosylphosphatidylinositol (GPI) moiety
[1–3].
Because of their abundance, the same TcMUC spe-
cies have been detected in many laboratories and given
different names. It was not until 1993 that these
molecules were identified as mucin-like glycoproteins
because their overall sugar and amino acid composition
resembled that of mammalian mucins [1–4]. The Tc-
MUC were first described by Alves and Colli in 1975 as
glycoproteins A, B, and C in noninfective epimastigotes
[5]. They were detected by SDS-PAGE and stained by
the periodic acid Schiff method. In addition, these
authors detected another major glycoconjugate with a
higher mobility in SDS-PAGE, named band D, which
was later characterized as a lipophosphopeptidoglycan
(LPPG) [6–8] and is currently known as glycoinosi-

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PII: S0166-6851(01)00245-6
144 A. Acosta-Serrano et al. / Molecular & Biochemical Parasitology 114 (2001) 143–150
tolphospholipid (GIPL) [9]. The TcMUC were later
described in epimastigote forms as 43-kDa sialylated
glycoconjugates [10], as GP24, GP31 and GP37 cell-
surface glycoconjugates [11], and as 38/43-kDa glyco-
conjugates [3]. The so-called lipophosphoglycan-like
molecule [12] and the membrane antigen Ag– C10 [13]
probably also belong to the same family of molecules.
The TcMUC are also found in other life-cycle stages.
In infective metacyclic trypomastigotes, these glyco-
proteins were originally reported as the 35/50-kDa anti-
gens involved in attachment and cell invasion [14]. In
trypomastigote forms derived from infected mammalian
cells, the TcMUC were described as a group of
molecules that share the stage-specific epitope 3 (Ssp-3)
[15], an epitope dependent on parasite sialylation and
also involved in attachment and the host cell invasion
[16]. The same family of glycoproteins was identified
later as the main target for recognition by chronic
Chagas’ disease anti-a-galactosyl antibodies [2]. It is
unknown whether amastigotes, the replicative intracel-
lular forms of T. cruzi, express mucins on their surface.
However, a group of highly abundant GPI-anchored
molecules with structural features similar to the Tc-
MUC have been identified in this parasite stage [17].
Mucins have also been detected in parasites isolated
from the insect vector Triatoma infestans [18].
One striking feature of the TcMUC is that they
represent the major acceptors of sialic acid (SA) of the
cell-surface trans-sialidase (TS) (for reviews on TS see
[19,20]). SA is transferred to O-glycans and sialylation
of the parasite surface occurs in all developmental
stages except amastigote forms, which lack TS activity
[21]. As we will discuss later, the acquisition of SA
appears important for parasite infectivity and for its
survival in the vertebrate host [19].
In the past few years substantial information regard-
ing the structure, function, and the gene organization of
the TcMUC has been obtained. In the following sec-
tions we describe these recent advances, giving empha-
sis to the structure and possible biological roles of this
group of T. cruzi surface molecules. Some of these
aspects have been recently reviewed elsewhere [22].
2. Stage-specific features of the TcMUC
2.1. Structure of the O-linked oligosaccharides
The primary structure of the TcMUC O-linked gly-
cans has been solved in both epimastigotes and meta-
cyclic trypomastigotes from different strains [3,23,24].
Mucins from both stages contain the same type of
oligosaccharides after metacyclogenesis [23]. The most
relevant structural feature of the TcMUC glycosylation
is that their glycans are linked to Thr/Ser residues in
the protein core via N-acetylglucosamine (GlcNAc)
rather than N-acetylgalactosamine as usually found in
vertebrate mucins. It is also unusual that in some
strains about 20% of the total O-GlcNAc is non-substi-
tuted, whereas the remainder can be substituted by one
or up to five galactose residues, in a parasite strain-de-
pendent manner. Most of the Gal residues are present
as b-galactopyranose (bGalp) linked as linear and
branched side-chains to the 4- and 6-positions of the
GlcNAc. In some strains a b-galactofuranose residue
can also be linked to the 4-position of the GlcNAc
[3,23]. Although all terminal bGalp residues are poten-
tial acceptors for SA, in vitro studies have shown that
some oligosaccharides cannot be sialylated, probably
due to steric hindrance [3,23].
Mucins from mammalian stage trypomastigotes do
not appear to contain single O-GlcNAc residues but
instead they have more complex oligosaccharide struc-
tures that can also contain a terminal SA. A striking
difference between the TcMUC O-glycans from insect
stages and that from mammalian stages is that the
latter can be alternatively a-galactosylated at the non-
reducing end [2]. The major a-galactosylated oligosac-
charide is Gala1-3Galb1-4GlcNAc but branched
structures containing both terminal a- and b-Galp
residues are also found [2]. These a-galactosylated
oligosaccharides are highly immunogenic to humans
under conditions of natural infection and, in fact, rep-
resent the major target for trypanolytic anti-aGal anti-
bodies from acute and chronic Chagasic patients
[2,25,26]. Other less abundant surface glycoproteins,
from the same parasite stage, also contain terminal
a-Gal residues but in N-linked glycans [27].
2.2. Biosynthesis of the O-linked glycans
Very little is known about the biosynthesis of the
Tc-MUC O-glycans. The only report concerns about
the biochemical characterization of a uridine diphos-
pho-N-acetylglucosamine:polypeptide-a-N-acetylgluco-
saminyltransferase activity [28]. This enzyme transf-
ers GlcNAc residues to the synthetic peptide
KPPTTTTTTTTKPP (a sequence similar to one
present in some members of the TcMUC family [29,30],
see below), but not to the peptide YSDSPSTST, sug-
gesting that it differs from the well characterized cyto-
solic mammalian O-GlcNAc transferase [31]. In
addition, the candidate TcMUC GlcNAc transferase is
strongly inhibited by UDP, is insensitive to both tu-
nicamycin and amphomycin, and is found exclusively in
the microsomal fraction. All these features suggest that
this enzyme may be responsible for transfer of GlcNAc
residues during synthesis of the TcMUC O-glycans.
However, since the potential targets of GlcNAc addi-
tion are located in the highly variable central domains
of the polypeptide (some of them containing Ser-rich
regions instead of Thr repeats; see below), it is possible
 A. Acosta-Serrano et al. / Molecular & Biochemical Parasitology 114 (2001) 143–150 145

that more than one GlcNAc-transferase is involved in
the synthesis of the TcMUC O-glycans.
2.3. Structure of the GPI-anchors
T. cruzi mucins have GPI anchors whose lipid moiety
is developmentally regulated. Mass-spectrometry analy-
ses show that the phosphatidylinositol (PI) moiety from
epimastigote mucins contains exclusively alkylacyl-PI
species (mainly 1-O-hexadecyl-2-O-hexadecanoyl-PI)
[23,32] whereas metacyclic mucins have predominantly
inositol-phosphoceramides [23] (Fig. 1A and B). These
ceramide-PI species contain a C18:0-sphinganine chain
and mainly C24:0 and C16:0 fatty acids. As for the
mammalian-cell derived trypomastigote mucins, the PI
moiety is composed exclusively of alkylacyl-PI struc-
tures [33,34]. However, in contrast to the epimastigote
mucins, most of these species ( 75%) contain unsatu-
rated fatty acids (C18:1 and C18:2) (Fig. 1C). As dis-
cussed below, it is amazing that such subtle differences
in the type of fatty acid strongly associate with the
ability of the trypomastigote mucins to induce secretion
of proinflammatory cytokines and nitric oxide by IFN-
g-primed murine macrophages [33–35].
The biological role of the ceramide anchor in meta-
cyclic trypomastigote mucins remains unknown. How-
ever, it is worth mentioning that most metacyclic
mucins are capped and locally shed by the parasite
during host cell invasion, whereas other alkylacyl-PI
cell surface glycoproteins (such as gp90 or 1G7 antigen)
remain attached to the parasite surface during this
process [1]. It is therefore possible that the surface
stability during invasion may be modulated by the
nature of the lipid of specific cell surface molecules.
Consistent with this hypothesis is the fact that TS from
trypomastigote stages, which also has a ceramide-based
GPI anchor, is constantly shed by the parasite both in
vitro and in the vertebrate host [36]. The mechanism
controlling the presence of a different lipid moiety in
the GPI anchor of epimastigote and metacyclic mucins
is unknown. One possibility, shown to occur in S.
cere6isiae [37], is that there is a GPI lipid remodelling,

Fig. 1. Schematic representation of the GPI anchors of the TcMUC from different life-cycle stages. Only the major species are shown. All TcMUC
GPI anchors (A – C) are composed of the same linear glycan core Mana1– 2Mana1– 2Mana1– 6Mana1– 4GlcN (represented by four gray circles
and a dotted square), but only that from cell-derived trypomastigotes can be modified by a branch of Gal residues (C). The exact location of these
Gal residues is not known. Note the presence of a different lipid moiety in the GPI anchor of the TcMUC from different developmental stages.
EtNP/2-AEP stands for ethanolamine phosphate and aminoethylphosphonate respectively. See text for other structural details. (A) Epimastigote;
(B) metacyclic trypomastigotes, and (C) cell-derived trypomastigotes.
146 A. Acosta-Serrano et al. / Molecular & Biochemical Parasitology 114 (2001) 143–150

Fig. 2. Diagram showing the possible types of TcMUC expressed on the surface of T. cruzi. This model is hypothetical and was drawn based on
the apparent molecular mass of isolated TcMUC and the abundance of the different TcMUC families in different stages of the parasite (see text
for details). The diagram shows the surface of different parasites expressing: (A) TcMUC containing the T(6 – 8)KP(1 – 2) repeats (family I); (B)
TcMUC containing variable N-terminal domains (family II), and (C) TcMUC family III.

and some evidence for the presence of such a pathway
in T. cruzi has been recently published [38].
The structure of the mucin GPI glycan also varies in
the different parasite stages. In the epimastigote and
metacyclic mucins the GPI glycan core is mainly com-
posed of the linear structure Mana1 – 2Mana1 –
2Mana1 –6Mana1 –4GlcN (Fig. 1A-B) [23,32]. In
contrast, those present in cell-derived trypomastigotes
can be larger, containing a branch of Gal residues up to
eight units in length [34] (Fig. 1C). Interestingly, all
mucin GPI glycan cores can also be substituted at the
third aMan (distal to the GlcN residue) and at the
GlcN residue by either ethanolamine phosphate and/or
2-aminoethylphosphonate (2-AEP) groups [23,32,34].
The presence of 2-AEP in the TcMUC GPIs, especially
in the linkage between the GPI and the polypeptide, is
striking and so far unique for a GPI-anchored protein.
However, 2-AEP is a well known component in T. cruzi
GIPLs [7 – 9].
3. The TcMUC are encoded by a multigene family
SDS-PAGE analyses have demonstrated that the Tc-
MUC differ in size depending on the stage of the
parasite. For instance, both epimastigote and meta-
cyclic trypomastigote forms express protease-resistant
mucins that migrate as two– three bands of about 35/
50-kDa (depending on the parasite strain) [39,40]. On
the other hand, mucins from mammalian trypomastig-
otes are partially sensitive at the C-termini to some
proteases, and they appear to be larger, migrating in
SDS-PAGE as diffuse bands between 60 and 200 kDa
[2,16,40]. Although differences in the degree of glycosy-
lation exist between TcMUC from different develop-
mental stages, the differences in size and sensitivity to
proteolytic cleavage may also be due to the expression
of stage-specific mucin gene products. In fact a large
polymorphic group of genes (about 500 per haploid
genome) seems to encode the TcMUC [29,30,41,42]. All
the TcMUC genes encode proteins containing conven-
tional signal peptides and GPI anchor addition sites,
whereas the central regions are highly variable. These
central domains contain the sites for GlcNAc addition
which may or may not be organized in tandem arrays
of a variable number of repeat units, coding for at least
two type of consensus sequences (named in the order
they were discovered): T(6 – 8)KP(1 – 2) (family I), and
KNT7ST3S(S/K)AP and DQT17 – 20NAPAKDT5-
7NAPK (family III; also called subfamilies L and S
respectively [30]). Alternatively, some gene products
contain central regions still rich in Thr, Ser and Pro
residues but not organized in repeated sequences (fam-
ily II).
3.1. De6elopmental expression of the TcMUC genes
Whether every TcMUC gene is expressed is un-
known, but recent data suggest that there must be
stage-specific mechanisms that regulate the expression
of mucin polypeptides in T. cruzi. Hybridization analy-
ses using RNA extracted from different developmental
stages of the parasite show that family I of TcMUC
genes (whose products have the T(6 – 8)KP(1 – 2) repeat
sequence) is expressed preferentially in the mammalian
stages. In contrast, those genes with heterogeneous
internal sequences (family II) are transcribed in variable
amounts in all stages of the parasite life-cycle [42].
Therefore, the presence of several T(6 – 8)KP(1 – 2) repeats
in the mucins of trypomastigotes derived from mam-
malian cells should provide several targets for O-glyco-
sylation and consequently, potential sialic acid acceptor
sites. This finding could explain why mammalian stage
mucins are more glycosylated and larger in size than
those expressed in insect forms [40]. A schematic repre-
sentation of these mucins is shown in Fig. 2A. The
 A. Acosta-Serrano et al. / Molecular & Biochemical Parasitology 114 (2001) 143–150
expression of TcMUC with non-repeated domains
could result in a large number of glycoproteins with
poorly glycosylated hypervariable N-terminal domains
(Fig. 2B). Recent data show that mRNAs from genes of
family III, which encode for small mucin polypeptides
(calculated molecular mass about 7 kDa), are highly
abundant in epimastigote forms and are stabilized by
the presence of AU-rich elements in the 3% UTR [30].
These findings strongly suggest that family III may be
abundantly expressed in the insect stages, which would
be consistent with the small size of the TcMUC in these
forms of the parasite. Such a hypothesis is strongly
supported by sequence analysis of the N-termini of
mucins isolated from epimastigote forms, which reveals
a high degree of homology with the predicted amino
acid sequences of the cDNA clones from family III
(ICA and MAJ Ferguson, unpublished observations).
Nevertheless, since the expression of the TcMUC can
potentially be regulated by both post-transcriptional
and post-translational mechanisms, as found in other
T. cruzi cell surface molecules [43], the differential
expression of specific families of TcMUC in different
stages of the parasite life cycle remains speculative. A
detailed analysis of the TcMUC polypeptides by mass
spectrometry may help to solve this puzzle.
4. Mucins are involved in T. cruzi invasion
There is strong evidence that the TcMUC play an
important role in the recognition and invasion of mam-
malian cells, although the mechanisms for this are still
unclear. In metacyclic trypomastigotes, carbohydrate-
specific monoclonal antibodies and the purified mucin
itself, can inhibit parasite entry [14,44]. In addition,
during host cell invasion the metacyclic mucins are
capped and extensively released in the parasitophorus
vacuole [1]. More recently, it was shown that purified
mucins are able to trigger Ca2 + signals in target cells
[45], an event associated with the early stages of host
invasion (reviewed in [46]). Interestingly, both the Ca2 +
signals in the host cells, as well as the ability of meta-
cyclic forms to enter HeLa cells, increase upon treat-
ment of parasite with neuraminidase [47]. This suggests
that SA residues on the surface of metacyclic trypo-
mastigotes either inhibit the parasite interaction with
the cell or down-regulate an important event required
for invasion. One possibility is that the metacyclic
trypomastigote mucin influences the relay of the signal
that leads to an increase in the parasite intracellular
Ca2 + concentration [48] which is required for target
cell invasion [49]. At present, the mechanism by which
the metacyclic trypomastigote mucin molecule trans-
duces external signals to the parasite interior is not
clear. Perhaps the metacyclic mucin interacts with other
metacyclic surface glycoproteins such as Tc-85 or gp82,
147
which are also involved in cell invasion [48,50– 52]. As
a Ca2 + response is not detectable in epimastigotes, one
intriguing possibility is that the nature of the lipid
moiety of the GPI anchor may influence the ability of
mucins to interact with plasma membrane components
associated with the downstream molecules of the signal-
ing cascade, either in the parasite or host cells.
In trypomastigotes derived from infected mammalian
cells, the degree of mucin sialylation has little or no
effect on invasion [53], although antibodies directed to
the mucins inhibit parasite entry [54]. Invasion depends
instead on the degree of sialylation of the host cell
[53,55,56]. The opsonization of trypomastigotes with
anti-mucin antibodies, but not with antibodies to other
cell surface molecules of T. cruzi, prevents invasion of
these parasites to non-phagocytic cells transfected with
Fc receptors, suggesting that the TcMUC participate in
the entry process [57].
The apparently contradictory role of the TcMUC in
host cell invasion by different forms of T. cruzi suggests
that these molecules might cooperate with other surface
molecules in the events of adhesion and internalization.
For instance, it is intriguing that TS from insect-derived
trypomastigotes is much less active than that from
cell-derived trypomastigotes (0.03 vs 1 U/107 parasites,
respectively). As the degree of sialylation per se does
not account for invasion, the large amount of TS in
cell-derived trypomastigotes — some without hy-
drolytic, or transfer activity, but with acceptor binding
capability [58] — might suggest a cooperative effect
between TS and TcMUC in mediating interactions with
the host cells.
5. The TcMUC as potent stimulators of
proinflammatory macrophages
Trypomastigotes derived from infected mammalian
cells (as well as extracts from this stage of the parasite)
but not those corresponding to insect derived forms,
are powerful inducers of the synthesis of proinflamma-
tory cytokines (e.g. IL-12 and TNF-a) and nitric oxide
by macrophages [59–61]. Analysis of parasite mem-
brane components led to the identification of mucins as
being responsible for this biological activity [33–35].
The lipid moiety of the GPI anchor of the TcMUC
from cell-derived trypomastigotes (specifically those
with unsaturated fatty acids at the sn-2 position of the
glycerol moiety) and periodate-sensitive residues (e.g.
GPI glycans), are the major components involved
[34,35]. In contrast, purified TcMUC (or GPI frag-
ments) from both epimastigote and metacyclic trypo-
mastigote forms, which contain alkylacyl-PI (with
saturated fatty acids) and ceramides respectively (see
above), are very poor activators of macrophages. It is
possible that the strong immunological activity induced
148 A. Acosta-Serrano et al. / Molecular & Biochemical Parasitology 114 (2001) 143–150
by the cell-derived trypomastigote TcMUC, at a sub-
nanomolar range, is related to the excessive cell-medi-
ated immunity, which causes host tissue damage and
death during the chronic phase of Chagas’ disease.
Purified GPI anchored-glycoconjugates from amastig-
ote forms are also good activators of monokine synthe-
sis [17], although the structural basis of this activation
has not yet been characterized.
6. Protective role of the TcMUC
The TcMUC are expressed in large amounts in all
stages of the T. cruzi life cycle as a major surface
component of the parasite. Only in epimastigotes does
LPPG seem to be present in higher copy number
[62,63]. Because of their abundance ( 2 × 106 per par-
asite) and their high resistance to proteases and glycosi-
dases [23,39], the TcMUC form a protective coat that
covers the entire parasite surface. The presence of such
protective shield may be important for parasite devel-
opment and growth in the insect vector, surviving the
action of digestive enzymes. Under these circumstances
it is worth mentioning that SA residues may not play
any role since a powerful a2-3-specific sialidase activity
in the insect gut removes most of the SA from the
parasite surface [18]. In addition, in metacyclic trypo-
mastigote forms, which successfully initiate infection of
the mammalian gastrointestinal tract [64], the protease-
resistant TcMUC may confer the ability to survive to
extreme low pH and the proteolytic enzymes present in
gastric secretion.
The TcMUC may also play an important protective
role in the vertebrate forms and in this case, an effective
sialylation of the parasite seems to be critical. When the
mucins are sialylated, each parasite acquires about 1×
107 SA residues, resulting in a strong negative charge
on the surface. This negatively charged coat is thought
to protect against complement-independent lysis in-
duced by human anti-a-galactosyl antibodies [26]. The
protection mechanism apparently relies on the preven-
tion of membrane damage induced by capping, with SA
providing lateral repulsion between mucin molecules
[63]. Sialylation could also affect the interaction of
parasites with host receptors by a similar mechanism.
Sialylation however, has little effect on the protection
against complement-dependent lysis [65], which is ac-
complished by another set of T. cruzi surface proteins
[66].
The high variability of mucin polypeptides could
have an additional protective effect against the host
immune system. In fact, hypervariable regions located
in the TcMUC N-termini of some members are recog-
nized by sera from infected hosts [67]. This antigenic
diversity could resemble the mechanism of antigenic
variation found in other parasites.
7. Concluding remarks
Many exciting aspects of TcMUC remain to be ex-
plored in future research. For instance, what is the
function of parasite mucins in the interaction with the
insect vector? Are the differences in structure, composi-
tion and abundance of the TcMUC from the mam-
malian stages associated with the infectivity pattern,
virulence, or tissue tropism? Very little is known about
the TcMUC gene regulation and biosynthesis. Because
the TcMUC are unique and structurally very different
from the mammalian mucins, studies on the biosynthe-
sis of these molecules could lead to the identification of
new glycosylation pathways helpful in the discovery of
highly specific targets for chemotherapy.
Acknowledgements
This work was supported by grants from CNPq and
FAPESP (Brazil). AAS was supported in part by
CONICIT (Venezuela) and by NIH grant AI21334 (to
Paul Englund), and is currently a Wellcome Trust
Travelling Research Fellow. For ICA is a Research
Fellow from CNPq and is supported by a grant from
FAPESP (1998/10495-5). We thank Paul Englund, Lys
Guilbride, Marı́a Julia Manso Alves, Ernesto Marques
and Terry Shapiro for critical reading of the manuscript
and helpful suggestions, and Javier Di Noia and Carlos
Frasch for providing data before publication.
Note added in proof
During submission of this paper, another review
article on the TcMUC was published by A. Frasch
(Parasitol. Today 16, 282–286, 2000). This review con-
tains more updated information on the TcMUC protein
families.
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