The document provides an overview of cell signaling and signal transduction. It discusses how cells communicate with each other via signaling molecules, both over short and long ranges. The key modes of cell signaling are introduced as autocrine, paracrine, endocrine, and juxtacrine signaling. The document then examines the processes of signal transduction, how signals are transmitted across and within cells to elicit responses. Specific topics covered include the synthesis and release of signaling molecules, signal detection by receptors, and the cellular changes induced by receptor-signal complexes.

1. PRESENTED BYPRESENTED BY
V.Prem PrasadV.Prem Prasad
M.Pharmacy 1M.Pharmacy 1stst
Year(pharmacology)Year(pharmacology)
Gokaraju rangaraju college of pharmacyGokaraju rangaraju college of pharmacy 1

2. CONTENTS
 IntroductionIntroduction
 Modes of cell signalingModes of cell signaling
 Communication between cellsCommunication between cells
 Signal transductionSignal transduction
 Ion channelsIon channels
2

3. INTRODUCTION:
Cells must be ready to respond to essential signals in their environment. TheseCells 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 cellsnearby cells  cytokines;cytokines;
oror
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.
3

4. CELL SIGNALING
Cell signalingCell signaling is part of ais part of a complex systemcomplex system of communication that governs basicof 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 theThe 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 treatedautoimmunity, 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.
4

5. 5

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 membranesHow are signals transmitted across cell membranes
into cell interiorinto 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
6

7. 7

8. 8

9. SYNTHESIS OF SIGNALLINGSYNTHESIS OF SIGNALLING
MOLECULESMOLECULES
RELEASE OF SIGNALLING MOLECULESRELEASE OF SIGNALLING MOLECULES
TRANSPORT OF SIGNAL TO TARGETTRANSPORT OF SIGNAL TO TARGET
CELLSCELLS
DETECTION & BINDING OF SIGNAL BY SPECIFIC RECEPTORDETECTION & 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
9

10. CLASSIFICATION OF INTERCELLULARCLASSIFICATION 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 cellssignals 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 areclose 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. neurotransmitterssignals 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 travelsignals 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 transmittedsignals target adjacent (touching) cells. These signals are transmitted
along cell membranes via protein or lipid components integral to the membrane and arealong 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.
10

11. 11

12. 12

13. 13

14. JUXTACRINE SIGNALING
MEMBRANE-ANCHOREDMEMBRANE-ANCHORED
LIGANDSLIGANDS
NEIGHBOURINGNEIGHBOURING
CELLSCELLS
14
e.g.*Notch signalling.e.g.*Notch signalling.

15. 15

16. 16

17. 17

18. 18

19. 19

20. 20

21. 21

22. 22

23. 23

24. 24

25. 25

26. 26

27. 27

28. 28

29. 29

30. 30

31. Ion Channels
31

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.
32

33. Cell membrane
33

34. Membrane transport proteins
34

35. Only ion channels have an aqueous pore that crosses theOnly ion channels have an aqueous pore that crosses the
membranemembrane
Ion channels are not pumps
35

36. Channels are made up of subunits
 Ion channels are made from 2-6 similar proteins or homologousIon channels are made from 2-6 similar proteins or homologous
structural units ‐ PORE-FORMING SUBUNITS - they associate creatingstructural 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
36

37. Channels are made up of subunits
 Pore-forming subunits contain anPore-forming subunits contain an αα‐helix made by ~20 hydrophobic‐helix made by ~20 hydrophobic
amino acids which interact with the annular phospholipids of the lipidamino acids which interact with the annular phospholipids of the lipid
bilayerbilayer
37

38. Ion channel types (by gating)
38

39. Ligand-gated channels
Typically, these are ion channels located on the postsynapticTypically, 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 aSome 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 metabolitescGMP and cAMP, and are also regulated by internal metabolites
such as phosphoinositides, arachidonic acid, calcium.such as phosphoinositides, arachidonic acid, calcium.
39

40. Signal-gated channels
Atrial m2 receptor-G protein-Atrial m2 receptor-G protein-
coupled Kcoupled K++
channelschannels
40

41. Modifiers of Channel Gating
(curare)(curare)
(ACh)(ACh)
(alpha-(alpha-
bungarotoxin)bungarotoxin)
Binding of exogenous ligandsBinding of exogenous ligands
can block gatingcan block gating
41

42. Modifiers of Channel Gating
Ion permeation can beIon permeation can be
prevented by pore blockers,prevented by pore blockers,
e.g. voltage-dependente.g. voltage-dependent
block of NMDARs by Mgblock of NMDARs by Mg2+2+
42

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
43

44. Bu Z, Callaway DJ (2011). "Proteins MOVE! Protein dynamics and long-range allosteryBu 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 onCongreve 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
44

45. 45

46. 46