Lecture 2: Cellular signalling and cell division
Cellular signalling:
Evolution of social behaviour in cells
Cell to cell communication and responses are essential for the organism as
whole.
Different types of cell signalling: synaptic
Endocrine
Paracrine
Autocrine
Cell to cell signalling by direct contacts: a) via receptors b) via gap junctions
and plasmadesmata
Extra-cellular signals: Hormones
Cytokines
Growth factors
Signalling Mechanisms:
1. Receptor enzyme mediated
2. G-protein linked Receptor mediated
3. Ion-channel-linked Receptor mediated
4. Intra-cellular Receptor mediated
Receptor enzyme mediated:
Receptor tyrosine kinases
Examples- receptors for most of growth factors e.g. FGF, PDGF, Insulin, IGF1, CSF
Binding of ligand to RTK----activation of TK activity------autophosphorylation----binding of GTPase activating protein or PI3 kinase or phospholipase---Activation of PKC and/or Ras---activation of MAPKKK----activation of
MAPKK---Activation of MAPK----c-Jun---activation of transcription
Receptor serine/threonine kinases:
Examples- TGF-family of receptors
G-protein linked receptor mediated Signalling:
Examples- adrenalin,Calcitonon, oxytosin, acatylcholine, dopamine,
histamine, PTH, retinal, serotonin etc.
Binding to receptor -----conformational change in G-protein complex-----GGTP formation-----activation of adnylate cyclase-----production of camp--activation of protein kinase A (camp dependent kinase)-----
Ion channel-linked Receptors:
Neurotransmitter receptors
NMDA receptors, serotonin, acetylcholine receptors etc
Binding----opening of ion channel------influx of Na, or K or Ca ions---downstream events
Drugs: barbiturates, antidepressants used a blockers
Intra-cellular Receptors
Mostly steroid hormone receptors: Cortisol, estrogen, progesterone,
thyroid hormone, retinoic acid, vitaminD
Binding to receptor---- exposure of DNA-binding site, and NLS---activation of transcription
NO signalling:
Recently discovered as signalling molecule.
Diffuses through plasma membrane rapidly and binds to Gunylate cylase.
Binding to heme group of gunylate cyclase
Activation
production of
cGMP
activation of downstream enzymes
Causes muscle relaxation, involved in release of neurotransmitters, at
high level neurotoxic.
Cell division: The fundamental principle of life
Interphase: cells look normal and just grow insize as observed under
microscope. But many molecular events take place in this phase and this phase
further subdivided into following subdivisions:
G1 phase: Starts after completion of mitosis and ends before beginning of
DNA synthesis. Important decision to start cell cycle is made in the late G1
phase.
S phase: This phase is marked by the start and completion of DNA
replication.
G2 phase: Cells prepare for cytoplasmic events for cell division and make
sure that there is appropriate conditions before entering the M phase.
Mitotic phase: Visible changes in the cells
Check points in cell division cycle
Cell cycle control: M-phase promoting factor – a complex of ser/thr kinase
called cyclin-dependent protein kinase Cdk-2 or cdc2 and a mitotic cyclin
Synthesis and destruction of cyclins control the activity of MPF.
Re-replication block
Growth factors trigger cascade of intracellular signals
Growth factor binding---activation of TK-----activation of MAPKKK-------transcription of myc gene-----transcription of Cdk and cyclins
Mitosis
Prophase
Metaphase
Anaphase
Telophase
Cytokinasis
Remember that DNA replication takes place in prophase and DNA is packed into
a condensed form called chromosomes. Each chromosome has two chromatids,
and during metaphase and telophase, each chromatid separates and daughter
cells have the same number of chromosomes.
Meosis:
Prophase I---subdivided in to 5 stages
Leptotene---Chromatids are formed, Chromosomes look like treads
Zygotene----Homozygous chromosome come close forming pairs
Pachetene---further condensation of chromosomes
Diplotene---Completion of pairing of chromosomes (completely aligned
chromosomes)
Dikinasis---chromosomes separate, and chromatids are attached at the places
of crossing over or chiasma. (chromosomes look like garlands)
Metaphase I
Anaphase I
(separation of chromosomes and not the chromatids)
Telophase I
Meotic division II: same as usual mitosis