What is Cell Biology?

What is cell signaling
Why do we study Cell Biology
Classification of the cells?
Comparative analysis of the different cells

Significant Events in Cell Biology

There have been several significant events throughout history that have led
to the development of the field of cell biology as it exists today. Below are a
few of these major events:1655 - Robert Hooke gives first description of a
cork tree cell.
1674 - Leeuwenhoek views protozoa.
1683 - Leeuwenhoek views bacteria.
1831 - Robert Brown was first to identify the nucleusas an important cell
component.
1838 - Schleiden and Schwann introduce what would become the Cell
Theory.
1857 - Kolliker describes mitochondria.
1869 - Miescher isolates DNA for the first time.
1882 - Kock identifies bacteria.
1898 - Golgi discovers the Golgi apparatus.
1931 - Ruska builds the first Transmission Electron Microscope.
1953 - Watson and Crick propose structure of DNA double-helix.
1965 - First commercial Scanning Electron Microscope produced.
1997 - First sheep cloned.
1998 - Mice cloned.
2003 - Human genome DNA sequence draft completed.
http://biology.about.com/od/cellbiology/a/cellbiology.htm
1.Cellular Signaling: General principles of signaling by cell surface receptors,
endocrine, paracrine and autocrine signaling, types of cellular responses
induced by signaling molecules, components of intracellular signal-transudation
pathways.

2. Short Term Signaling: G-protein coupled receptor system, General mechanism
of the activation of effectors molecules associated with G-protein-coupled
receptors, G-protein coupled receptors that activate or inhibit adenylate cyclase,
G-protein coupled receptors that activate phospholipase C, and G-protein
coupled receptors that regulate ion channels.

Cell Biology-II
LS-1&2


Sense, amplify and response (genetic, biochemical, physiological)

Autocrine, paracrine, endocrine and intracrine (Steriods)

Autocrine and paracrine signaling leading to stimulation of tumor cell growth is a common
process in human cancers.

Dynamic, short term and long term cellular responses

Signaling molecule: DNA, RNA, Protein, Small molecules, gaseous molecule, Photon,
mechanical forces etc


Input (receptor), processor (transducer) and output (effectors)

A prototypical neuropeptide receptor is depicted that couples to
the indicated signaling pathways through Gq and G12,13 proteins.
Signal pathways regulated by neuropeptide receptors.
Interruption of autocrine and paracrine neuropeptide signaling with specific
antagonists or broad-spectrum biased agonists offer promising new
therapeutic approaches to the treatment of human cancers.
Oncogene (2001) 20, 1563 -1569
Autocrine or paracrine signals also activate intrinsic growth-factor receptor tyrosine
kinases, and cytokine-receptor associated Janus-family kinases (JAKs) and SRC
family tyrosine kinases, which, in turn, phosphorylate signal transducer and activator
of transcription 3 (STAT3).

In transformed cells, STAT3 can also be activated by constitutively active non-receptor
tyrosine kinases such as SRC and ABL.

After tyrosine phosphorylation, STAT3 molecules dimerize and translocate to the
nucleus, where they directly regulate gene expression.

STAT3 signaling is normally tightly regulated by several inhibitory molecules, including
suppressor of cytokine signalling (SOCS) proteins, protein inhibitor of activated STAT
(PIAS) proteins and protein tyrosine phosphatases (PTPases).

In cancer cells, however, overactive receptor and non-receptor tyrosine kinases cause
persistent STAT3 phosphorylation and activation.
NATURE REVIEWS | IMMUNOLOGYVOLUME 7 | JANUARY 2007
Constitutive activation of STAT3 by receptor and non-receptor tyrosine kinases.

Basal Release of ATP: An Autocrine-Paracrine Mechanism for Cell Regulation
Cells release adenosine triphosphate (ATP), which activates plasma membrane–localized P2X
and P2Y receptors and thereby modulates cellular function in an autocrine or paracrine manner.

Release of ATP and the subsequent activation of P2 receptors establish the basal level of
activation (sometimes termed "the set point") for signal transduction pathways and regulate a
wide array of responses that include tissue blood flow, ion transport, cell volume regulation,
neuronal signaling, and host-pathogen interactions.

Basal release and autocrine or paracrine responses to ATP are multifunctional, evolutionarily
conserved, and provide an economical means for the modulation of cell, tissue, and organismal
biology.
R. Corriden, P. A. Insel, Basal Release of ATP: An Autocrine-Paracrine Mechanism for Cell Regulation.
Sci. Signal. 3, re1 (2010).
Prototype GPCR

Seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors
, serpentine receptor, and G protein-linked receptors.

Establish communication between environment and cellular side.

Integral membrane proteins.

The ligands that bind and activate these receptors include light-sensitive compounds, odors,
pheromones, hormones, and neurotransmitters, and vary in size from small molecules to peptides
to large proteins.

G protein-coupled receptors are involved in many diseases, and are also the target of around half
of all modern medicinal drugs.

GPCR signaling route-(a) Cyclase (b) Phosphatidylinositol-DAG-Kinase and PIP3-Receptors

GPCR+Ligand-Conformational changes-GEF-activation of G protein-Galpha-Effector-Outcome

Desensitization

Cycling of receptors


Class A (or 1) (Rhodopsin-like)-Subdivision for 19 group

Class B (or 2) (Secretin receptor family)

Class C (or 3) (Metabotropic glutamate/pheromone)

Class D (or 4) (Fungal mating pheromone receptors)

Class E (or 5) (Cyclic AMP receptors)

Class F (or 6) (Frizzled/Smoothened)
Classification of GPCR
Functional Importance
Immunity

Vision

Smell

Psychological

Aging-Population

Common structural component are responsible for wide physiological diversity.
Epinephrine-Glucose to Glucose-1-phosphate-Energy Metabolism

Epinephrine-β-adrenergic receptors (Heart, Smooth Muscles arteries)

Rise in cAMP
Prototype of GPCR and G-proteins Cycle
A Heterotrimeric G Protein
Gilman and Rodbell-Activation of enzyme indirectly
NP in 1994
Signaling molecule-Activation (Conformational change leads to GEF activity)-GTP
Termination- Hydrolysis of GTP with the help of GAP proteins

Conformational Changes in Gα On Nucleotide Exchange
G-protein families and their functions

Class Initiating signal Downstream signal
G
αs

β-Adrenergic amines, glucagon, parathyroid hormone, many
others
Stimulates adenylate cyclase
G
αi
Acetylcholine, α-adrenergic amines, many neurotransmitters Inhibits adenylate cyclase
G
αt
Photons
Stimulates cGMP
phosphodiesterase
G
αq
Acetylcholine, α-adrenergic amines, many neurotransmitters
Increases IP
3
and intracellular
calcium
G
α13
Thrombin, other agonists Stimulates Na
+
and H
+
exchange
Source: Z. Farfel, H. R. Bourne, and T. Iiri. N. Engl. J. Med. 340(1999):1012.
Diseases of heterotrimeric G proteins

Disease
Excessive signaling
Cholera
Cancer (adenoma) of pituitary and thyroid
Cancer (adenoma) of adrenal and ovary
Essential hypertension
Deficient signaling
Night blindness
Pseudohypoparathyroidism type Ib
Pertussis
Source: After Z. Farfel, H. R. Bourne, and T. Iiri. N. Engl. J. Med. 340(1999):1012.
Screening of potential drug molecule
Bioinformatics Advance Access published April 25, 2008
gpDB: A database of GPCRs, G-proteins, Effectors and their interactions.
Sequence variations in an adrenergic receptor gene cause reduced insulin secretion
and contribute to type 2 diabetes.
Ratting Out a Diabetes Gene
Paula A. Kiberstis
Sci. Signal. 3 (104), ec16. [DOI: 10.1126/scisignal.3104ec16]

Methods???