Cell surface and intrcellular receptors

TYPES OF RECEPTORS

1. Cell surface and intracellular
receptors and their role in signal
mediation (general
information)

2. SIGNAL RECEPTORS
•Theabilityofacelltorespondtoanextracellularsignaldependsonthe
presenceofspecificproteinscalledreceptors,whicharelocatedonthecell
surfaceorinthecytoplasm.
•
•Receptorsbindchemicalsignalsthatultimatelytriggeramechanismto
modifythebehaviourofthetargetcell.
•Cellsmaycontainanarrayofspecificreceptorsthatallowthemtorespond
toavarietyofchemicalsignals.
•Receptorsareproteinmoleculesinthetargetcelloronitssurfacethatbind
toligands.
•Therearetwotypesofreceptors,internalreceptorsandcell-surface
receptors.

3. INTERNAL RECEPTORS
•Internalreceptors,alsoknownasintracellularorcytoplasmic
receptors,arefoundinthecytoplasmoftargetcellsandrespond
tohydrophobicligandmoleculesthatareabletotravelacrossthe
plasmamembrane.
•Onceinsidethecell,manyofthesemoleculesbindtoproteins
thatactasregulatorsofmRNAsynthesis(transcription)to
mediategeneexpression.
•Geneexpressionisthecellularprocessoftransformingthe
informationinacell’sDNAintoasequenceofaminoacids,which
ultimatelyformsaprotein.
•Whentheligandbindstotheinternalreceptor,aconformational
changeistriggeredthatexposesaDNA-bindingsiteonthe
receptorprotein.

4. •Theligand-receptorcomplexmovesintothenucleus,thenbindstospecificregulatory
regionsofthechromosomalDNAandpromotestheinitiationoftranscription.
•
•TranscriptionistheprocessofcopyingtheinformationinacellsDNAintoaspecial
formofRNAcalledmessengerRNA(mRNA);thecellusesinformationinthemRNA
(whichmovesoutintothecytoplasmandassociateswithribosomes)tolinkspecific
aminoacidsinthecorrectorder,producingaprotein.
•Internalreceptorscandirectlyinfluencegeneexpressionwithouthavingtopassthe
signalontootherreceptorsormessengers.
•Hydrophobicsignalingmoleculestypicallydiffuseacrosstheplasmamembraneand
interactwithintracellularreceptorsinthecytoplasm.Manyintracellularreceptorsare
transcriptionfactorsthatinteractwithDNAinthenucleusandregulategene
expression.

6. Cell-surface receptors
•Cell-surfacereceptors,alsoknownastransmembranereceptors,are
integralproteinsthatbindtoexternalsignalingmolecules.
•Thesereceptorsspantheplasmamembraneandperformsignal
transduction,inwhichanextracellularsignalisconvertedintoan
intercellularsignal.
•Becausecell-surfacereceptorproteinsarefundamentaltonormalcell
functioning,itshouldcomeasnosurprisethatamalfunctioninany
oneoftheseproteinscouldhavesevereconsequences.
•Errorsintheproteinstructuresofcertainreceptormoleculeshave
beenshowntoplayaroleinhypertension(highbloodpressure),
asthma,heartdisease,andcancer.

8. COMPONENTS AND TYPES
•Each cell-surface receptor has three main components: an external
ligand-binding domain, or extracellular domain; a hydrophobic
membrane-spanning region; and an intracellular domain.
•Cell-surface receptors are involved in most of the signaling in
multicellular organisms.
•There are three general categories of cell-surface receptors:
•enzyme-linked receptors,
•ion channel-linked receptors
•G-protein-linked receptors.

9. ENZYME LINKED RECEPTORS
•Enzyme-linkedreceptorsarecell-surfacereceptorswithintracellulardomainsthatare
associatedwithanenzyme.
•Insomecases,theintracellulardomainofthereceptoritselfisanenzyme.
•Otherenzyme-linkedreceptorshaveasmallintracellulardomainthatinteractsdirectlywith
anenzyme.
•Enzyme-linkedreceptorsnormallyhavelargeextracellularandintracellulardomains,but
themembrane-spanningregionconsistsofasinglealpha-helixinthepeptidestrand.
•Whenaligandbindstotheextracellulardomainofanenzyme-linkedreceptor,a
signalistransferredthroughthemembrane,activatingtheenzyme.Activationofthe
enzymesetsoffachainofeventswithinthecellthateventuallyleadstoa
response.
•

10. Enzyme-linked receptor -tyrosine kinase receptor
•AkinaseisanenzymethattransfersphosphategroupsfromATPto
anotherprotein.
•Thetyrosinekinasereceptortransfersphosphategroupstotyrosine
molecules.
•First,signalingmoleculesbindtotheextracellulardomainoftwonearby
tyrosinekinasereceptors.
•Thetwoneighboringreceptorsthenbondtogether,ordimerize.
•Phosphatesarethenaddedtotyrosineresiduesontheintracellular
domainofthereceptors(phosphorylation).
•Thephosphorylatedresiduescanthentransmitthesignaltothenext
messengerwithinthecytoplasm.

12. •Epidermal growth factor receptors are an example of receptor
tyrosine kinases that follows this mode of signaling.
•Defects in ErbB signaling in this family can lead to
neuromuscular diseases such as multiple sclerosis and
Alzheimer’s disease.

13. Ion channel-linked receptors
•Ionchannel-linkedreceptorsbindtoaligandandopenachannel
throughthemembranethatallowsspecificionstopassthrough.
•Thistypeofcell-surfacereceptorhasanextensivemembrane-
spanningregionwithhydrophobicaminoacids.
•Conversely,theaminoacidsthatlinetheinsideofthechannelare
hydrophilictoallowforthepassageofions.
•Whenaligandbindstotheextracellularregionofthechannel,thereis
aconformationalchangeintheprotein’sstructurethatallowsions
suchassodium,calcium,magnesium,orhydrogentopassthrough

14. Ionchannel-linkedreceptorsopenandallowionstoenteracell.Anexampleofanionchannel-linkedreceptorisfoundon
neurons.Whenneurotransmittersbindtothesereceptors,aconformationalchangeallowssodiumionstoflowacrossthecell
membrane,causingachangeinthemembranepotential.

15. G-protein-linked receptors
•G-protein-linkedreceptorsbindtoaligandandactivatean
associatedG-protein.
•TheactivatedG-proteintheninteractswithanearbymembrane
protein,whichmaybeanionchanneloranenzyme.
•AllG-protein-linkedreceptorshaveseventransmembranedomains,
buteachreceptorhasaspecificextracellulardomainandG-protein-
bindingsite.
•CellsignalingusingG-protein-linkedreceptorsoccursasacycle.
•Oncetheligandbindstothereceptor,theresultantshapechange
activatestheG-protein,whichreleasesGDPandpicksupGTP.

16. •ThesubunitsoftheG-proteinthensplitintoαandβγsubunits.
•OneorbothoftheseG-proteinfragmentsmaybeableto
activateotherproteinsinthecell.
•Afterawhile,theGTPontheactiveαsubunitoftheG-proteinis
hydrolyzedtoGDPandtheβγsubunitisdeactivated.
•Thesubunitsre-associatetoformtheinactiveG-proteinandthe
cyclebeginsagain.
•G-proteinlinkedreceptorsareusedinmanyphysiological
processesincludingthoseforvisiontransduction,taste,and
regulationofimmunesystemandinflammation.

18. •http://utmadapt.openetext.utoronto.ca/chapter/9-2/
•https://rwu.pressbooks.pub/bio103/chapter/cell-communication/
•https://organismalbio.biosci.gatech.edu/chemical-and-electrical-
signals/intro-to-chemical-signaling-and-signal-transduction/