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The mechanism by which vesicles are recovered is thought to involve the HGNC 11504 (https://www.genen
synaptojanin attracting the protein clathrin, which coats the vesicle and initiates ames.org/data/gene-symb
vesicle endocytosis. ol-report/#!/hgnc_id/HGN
C:11504)
Synaptojanins are composed to three domains. The first is a central inositol 5-
OMIM 609410 (https://omim.org/
phosphatase domain, which can act on both PIP2 and PIP3. The second is an N-
609410)
terminal Sac1-like inositol phosphatase domain, which can hydrolyze to PI in
vitro PIP, PIP2. The third is a C-terminal domain that is rich in the amino acid RefSeq NM_003898 (https://geno
me.ucsc.edu/cgi-bin/hgTra
proline and interacts with several proteins also involved in vesicle cks?Submit=Submit&positi
endocytosis.[1] Specifically, the c-terminal domain interacts with amphiphysin, on=NM_003898&rn=1)
endophilin, DAP160/intersectin, syndapin and Eps15. The function of endophilin UniProt O15056 (https://www.unipr
appears to be a binding partner for synaptojanin such that it can interact with ot.org/uniprot/O15056)
other proteins and is involved in the initiation of shallow clathrin coated pits.
Other data
Dap160 is a molecular scaffolding protein and functions in actin recruitment.
Dynamin is a GTPase involved in vesicle budding, specifically modulating the Locus Chr. 6 q25.3 (https://omim.
severance of the vesicle from the neuronal membrane.[3] Dynamin appears to be org/search/?index=geneM
playing a larger role in neurite formation because its vesicle pinching role and ap&search=6q25.3)
the possibility of it recycling plasma membrane and growth factor receptor
proteins.[4]
Mutation in this gene have been associated with autosomal recessive, early-onset parkinsonism.[5]
Role in Development
Synaptojanin, through its interactions with a variety of proteins and molecules is thought to play a role in the development of
nervous systems.
Ephrin
Synaptojanin 1 has been found to be influenced by the protein ephrin.[6] Ephrin is a chemorepulsant meaning that its interactions
with proteins results in an inactivation or retraction of processes when referring to neuronal migration. Ephrin's receptor is called
Eph and is a receptor tyrosine kinase.[6] Upon activation of the Eph receptor, synaptojanin 1 becomes phosphorylated at the
proline rich domain and is inhibited from binding with any of its natural binding partners.[7] Therefore, the presence of ephrin
inactivates vesicle endocytosis.
Calcium
The influx of calcium in the neuron has been shown to activate a variety of molecules including some calcium dependent
phosphatases that activate synaptojanin.[8]
Membranes
Neuronal migration during development involves the extension of a neurite along the extracellular matrix. This extension is
guided by the growth cone. However the actual extension of the neurite involves the insertion of membrane lipids immediately
behind the growth one.[9] In fact, membranes can be trafficked from degenerating extensions to elongating ones.[10] Synaptojanin
has been proposed as the mechanism by which membrane lipids can be trafficked around the developing neuron.[9]
Receptors
During development, receptors are trafficked around the growth cone. This trafficking involves vesicle endocytosis. In the
presence of nerve growth factor (NGF), TrkA receptors are trafficked to the stimulated side of the growth cone.[8] Additionally,
calcium and glutamate stimulate the trafficking of AMPA receptors to the stimulated side of the growth cone.[11] Both of these
receptors are trafficked via synaptojanin.
Model organisms
Model organisms have been used in the study of Synaptojanin function. A
conditional knockout mouse line of synaptojanin 2, called Synj2 knockout mouse phenotype
External links
Synaptojanin (https://meshb.nlm.nih.gov/record/ui?name=Synaptojanin) at the US National Library of Medicine
Medical Subject Headings (MeSH)
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