Cell signaling

1. PRESENTED BYPRESENTED BY
V.Prem PrasadV.Prem Prasad
M.Pharmacy 1M.Pharmacy 1
stst
Year(pharmacology)Year(pharmacology)
Gokaraju rangaraju college of pharmacyGokaraju rangaraju college of pharmacy
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2. CONTENTS

IntroductionIntroduction

Modes of cell signalingModes of cell signaling

Communication between cellsCommunication between cells

Signal transduction Signal transduction

Ion channelsIon channels
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3. INTRODUCTION:
Cells must be ready to respond to essential signals in their environment. These Cells must be ready to respond to essential signals in their environment. These
are often chemicals in the extracellular fluid (ECF) from: are often chemicals in the extracellular fluid (ECF) from:
distant locations -distant locations - signaling by hormones; signaling by hormones;
nearby cells nearby cells  cytokines; cytokines;
or or
even secreted by themselves .even secreted by themselves .

Long-range allostery is often a significant component of cell signaling events. Long-range allostery is often a significant component of cell signaling events.
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4. CELL SIGNALING
Cell signalingCell signaling is part of a is part of a complex system complex system of communication that governs basic of communication that governs basic
cellular activities and coordinates cell actions.cellular activities and coordinates cell actions.
The ability of cells to perceive and correctly respond to their microenvironment is the The ability of cells to perceive and correctly respond to their microenvironment is the
basis of development, tissue repair, and immunity as well as normal tissue homeostasisbasis of development, tissue repair, and immunity as well as normal tissue homeostasis
Errors in cellular information processing are responsible for diseases such as cancer, Errors in cellular information processing are responsible for diseases such as cancer,
autoimmunity, and diabetes. By understanding cell signaling, diseases may be treated autoimmunity, and diabetes. By understanding cell signaling, diseases may be treated
effectively and, theoretically, artificial tissues may be created.effectively and, theoretically, artificial tissues may be created.
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6. CELL SIGNALING & SIGNAL
TRANSDUCTTION

Why do cells communicateWhy do cells communicate

How are signals transmitted between cellsHow are signals transmitted between cells

How are signals transmitted across cell membranes How are signals transmitted across cell membranes
into cell interior into cell interior

How are signals transmitted within a cellHow are signals transmitted within a cell

How do signals affect a cell functionHow do signals affect a cell function
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9. SYNTHESIS OF SIGNALLING SYNTHESIS OF SIGNALLING
MOLECULES MOLECULES
RELEASE OF SIGNALLING MOLECULES RELEASE OF SIGNALLING MOLECULES
TRANSPORT OF SIGNAL TO TARGET TRANSPORT OF SIGNAL TO TARGET
CELLSCELLS
DETECTION & BINDING OF SIGNAL BY SPECIFIC RECEPTOR DETECTION & BINDING OF SIGNAL BY SPECIFIC RECEPTOR
CHANGES DUE TO RECEPTOR-SIGNAL COMPLEXCHANGES DUE TO RECEPTOR-SIGNAL COMPLEX
SIGNAL REMOVAL & SIGNAL REMOVAL &
RESPNOSE TERMINATIONRESPNOSE TERMINATION



STEPS IN CELL SIGNALING
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10. CLASSIFICATION OF INTERCELLULAR CLASSIFICATION OF INTERCELLULAR
COMMUNICATIONCOMMUNICATION
Intercellular signaling is subdivided into the following classifications:Intercellular signaling is subdivided into the following classifications:
AutocrineAutocrine signals target the cell itself. Sometimes autocrine cells can target cells signals target the cell itself. Sometimes autocrine cells can target cells
close by if they are the same type of cell as the emitting cell. An example of this are close by if they are the same type of cell as the emitting cell. An example of this are
immune cells.immune cells.
ParacrineParacrine signals target cells in the vicinity of the emitting cell. neurotransmitters signals target cells in the vicinity of the emitting cell. neurotransmitters
represent an example.represent an example.
EndocrineEndocrine signals target distant cells. Endocrine cells produce hormones that travel signals target distant cells. Endocrine cells produce hormones that travel
through the blood to reach all parts of the body.through the blood to reach all parts of the body.
JuxtacrineJuxtacrine signals target adjacent (touching) cells. These signals are transmitted signals target adjacent (touching) cells. These signals are transmitted
along cell membranes via protein or lipid components integral to the membrane and are along cell membranes via protein or lipid components integral to the membrane and are
capable of affecting either the emitting cell or cells immediately adjacent.capable of affecting either the emitting cell or cells immediately adjacent.
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14. JUXTACRINE SIGNALING
MEMBRANE-ANCHORED MEMBRANE-ANCHORED
LIGANDSLIGANDS
NEIGHBOURING NEIGHBOURING
CELLSCELLS
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  e.g.*Notch signalling.e.g.*Notch signalling.

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31. Ion Channels
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32. Schematic diagram of an ion channel
1 - Channel domains(typically
four per channel),
2 - Outer vestibule,
3 - Selectivity filter,
4 - Diameter of selectivity filter,
5 - Phosphorylation site,
6 - Cell membrane.
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33. Cell membrane
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34. Membrane transport proteins
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35. Only ion channels have an aqueous pore that crosses the Only ion channels have an aqueous pore that crosses the
membranemembrane
Ion channels are not pumps
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36. Channels are made up of subunits
Ion channels are made from 2-6 similar proteins or homologous Ion channels are made from 2-6 similar proteins or homologous
structural units ‐ PORE-FORMING SUBUNITS - they associate creating structural units ‐ PORE-FORMING SUBUNITS - they associate creating
the functional ion channelthe functional ion channel
In addition, many channels contain the auxiliary regulatory subunitsIn addition, many channels contain the auxiliary regulatory subunits
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37. Channels are made up of subunits

Pore-forming subunits contain an Pore-forming subunits contain an aa‐helix made by ~20 hydrophobic ‐helix made by ~20 hydrophobic
amino acids which interact with the annular phospholipids of the lipid amino acids which interact with the annular phospholipids of the lipid
bilayerbilayer
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38. Ion channel types (by gating)
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39. Ligand-gated channels
Typically, these are ion channels located on the postsynaptic Typically, these are ion channels located on the postsynaptic
(receiving) side of the neuron(receiving) side of the neuron
Some act in response to a secreted (external) ligand- typically a Some act in response to a secreted (external) ligand- typically a
neurotransmitter such asneurotransmitter such as
•Acetylcholine (ACh)Acetylcholine (ACh)
•GABAGABA
•GlycineGlycine
•GlutamateGlutamate
Some act in response to internal ligands such as G-proteins, Some act in response to internal ligands such as G-proteins,
cGMP and cAMP, and are also regulated by internal metabolites cGMP and cAMP, and are also regulated by internal metabolites
such as phosphoinositides, arachidonic acid, calcium.such as phosphoinositides, arachidonic acid, calcium.
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40. Signal-gated channels
Atrial m2 receptor-G protein-Atrial m2 receptor-G protein-
coupled Kcoupled K
++
channels channels
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41. Modifiers of Channel Gating
(curare)(curare)
(ACh)(ACh)
(alpha-(alpha-
bungarotoxin)bungarotoxin)
Binding of exogenous ligands Binding of exogenous ligands
can block gatingcan block gating
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42. Modifiers of Channel Gating
Ion permeation can be Ion permeation can be
prevented by pore blockers, prevented by pore blockers,
e.g. voltage-dependent e.g. voltage-dependent
block of NMDARs by Mgblock of NMDARs by Mg
2+2+
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43. Modifiers of Channel Gating
Exogenous modulators can modify the action of endogenous ligandsExogenous modulators can modify the action of endogenous ligands
OpenOpen
ClosedClosed
OpenOpen
ClosedClosed
CurrentCurrent
TimeTime
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44. Bu Z, Callaway DJ (2011). "Proteins MOVE! Protein dynamics and long-range allostery Bu Z, Callaway DJ (2011). "Proteins MOVE! Protein dynamics and long-range allostery
in cell signaling". in cell signaling". Advances in Protein Chemistry and Structural BiologyAdvances in Protein Chemistry and Structural Biology. Advances in . Advances in
Protein Chemistry and Structural Biology Protein Chemistry and Structural Biology 8383: 163–221. : 163–221. 
Rang & Dale's PharmacologyRang & Dale's Pharmacology
http://en.wikipedia.org/wiki/Cell_signalinghttp://en.wikipedia.org/wiki/Cell_signaling
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellSignaling.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellSignaling.html
www.authorstream.com/.../shona6685-645587-www.authorstream.com/.../shona6685-645587-pptppt--cellcell--signalingsignaling
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC151254/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC151254/
  Congreve M, Marshall F (March 2010). "The impact of GPCR structures on Congreve M, Marshall F (March 2010). "The impact of GPCR structures on
pharmacology and structure-based drug design". pharmacology and structure-based drug design". Br. J. Pharmacol.Br. J. Pharmacol.  159159 (5): 986– (5): 986–
96.doi:10.1111/j.1476-5381.2009.00476x PMC 2839258 PMID1991223096.doi:10.1111/j.1476-5381.2009.00476x PMC 2839258 PMID19912230
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