3/15/15%1%1%7%18%13%20%19%26%31%43%38%37%2%3%4%8%5%44%9%14%15%36%11%10%22%21%27%33%34%39%23%24%29%42%35%30%41%16%17%32%Sit%in%the%area%marked%with%your%study%group%(secAon)%number%28%6%40%25%12%Cell%Signaling%I.%General%principles%%How%do%cells%communicate%with%one%another?%1. Be%able%to%describe%the%major%concepts%of%cellular%signaling.%2. Know%the%four%major%types%of%signaling%systems%in%animal%cells:%endocrine,%paracrine,%neuronal%and%contactQdependent.%3. Describe%the%difference%between%mechanisms%of%slow%and%fast%signaling.%4. Understand%the%two%types%of%signals%and%receptors:%those%that%cross%the%cell%membrane%(e.g.%gases%and%small%hydrophobic%molecules)%and%those%that%can’t%(e.g.%hydrophilic%or%large).%5. Understand%the%purpose%of%all%the%components%of%signal%transducAon%systems.%6. Know%the%three%main%classes%of%cell%surface%receptors:%ionQchannelQcoupled%receptors,%GQproteinQcoupled%receptors,%and%enzymeQcoupled%receptors.%Neutrophil%migraAon%in%response%to%chemical%signal%Reading:%%EC3B%531Q544;%ECB4%525Q538%LEARNING%GOALS:%3/15/15%2%Lecture'Summaries'instead'of'bullet'points:'%Available%a_er%each%lecture%on%Blackboard%under%“Lecture%Documents”%%Red,'bold,'underlinedQQQyou%should%be%able%to%write%out%definiAons%to%these%terms%or%phrases%and%understand%the%context%in%which%they%are%used.%%Readings:%ECB%as%assigned%Chapter%22%of%Molecular%Biology%of%the%Cell%(MBoC%–%Blackboard%website%under%Textbooks).%%%%Professor'Kemphues’s'Office'hours:''Thursdays'4:00PMB6:00PM'in'Room'106'SEmson'Hall.'%Differences'in'the'second'half'of'the'course'Developmental%Biology%Cell%communicaAon%3/15/15%3%Human%zygote%How%does%a%single%cell%become%a%funcAoning%organism?%How%do%cells%communicate%with%one%another?%What’s%up??%Would%you%please%stop%dividing??%3/15/15%4%Learning%goals:%%Major%concepts%of%cell%signaling%Four%types%of%signaling%mechanisms%Two%types%of%signals%and%receptors%Examples%of%signaling%by%molecules%that%pass%the%membrane.%Fast%vs.%slow%signaling%Components%of%signal%transducAon%systems%Three%classes%of%surface%receptors%%Cell%communicaAon%is%essenAal%>%7000%of%our%~25,000%genes%are%involved%in%cell%communicaAon%Cells%get%signals%from%their%environment%%light%%temperature%Nutrient%pressure%%%Other%cells%%%3/15/15%5%Figure 16-2 Essential Cell Biology (© Garland Science 2010) Cell%communicaAon%is%called%cell'signaling''The%conversion%of%an%extracellular%signal%into%an%interpretable%message%in%the%cell%is%called%signal'transducEon.%Most%signals%between%cells%are%molecular%(amino%acids,%pepAdes,%proteins,%lipids,%faky%acid%derivaAves,%steroids,%gases.)%Signal'(Ligand)'Receptor'signal transduction is the process whereby 1 type of signal is converted to another.3/15/15%6%Figure 16-3 Essential Cell Biology (© Garland Science 2010) Types%of%cell%signaling%Testosterone%Estradiol%Adrenaline%CorEsol'Insulin'EGF'NGF'PDGF%TGFQβ"Wnt%Hedgehog%NO%Glutamate'Glycine%GABA%Serotonin%Dopamine%Acetylcholine'Delta'(Notch)'CAMs%=%Juxtacrine%How%does%a%cell%know%which%signals%are%relevant?%Cells%can%only%respond%to%signals%for%which%they%have%receptors%and%appropriate%intracellular'signaling'molecules%for%transducing%the%signal.%%The%same%signal%can%elicit%different%responses%%a)%same%receptor%gives%different%response%in%different%cells%%b)%same%signal%can%acAvate%different%receptors%The%ability%of%a%cell%to%respond%to%a%parAcular%signal%depends%upon%its%developmental%history%and%current%state.%%endocrine: - produced in endocrine glands are secreted into the bloodstream and are distributed widely throughout the body paracrine: - signals are released by cells into extracellular fluid in their neighborhood and act locally synaptic: - neuronal signals are transmitted electrically along a nerve cell axon contact-dependent: - cell-surface-bound signal molecule binds to a receptor protein on an adjacent cell3/15/15%7%Figure 16-5 Essential Cell Biology (© Garland Science 2010) same%receptor:%different%response%same%signal%different%receptor:%different%response%Yummmmm!%- same signal molecule can induce different responses in different target cells - acetylcholine binds to similar receptor proteins on heart pacemaker cells and salivary gland cellssecretion->contraction -> acetylcholine3/15/15%8%Figure 16-5 Essential Cell Biology (© Garland Science 2010) same%receptor:%different%response%same%signal%different%receptor:%different%response%Figure 16-5 Essential Cell Biology (© Garland Science 2010) same%receptor:%different%response%same%signal%different%receptor:%different%response%acetylcholine binds to similar receptors on heart pacemaker cells and salivary gland cells, but it causes different responses in each cell type3/15/15%9%Figure 16-7 Essential Cell Biology (© Garland Science 2010) Responses%can%be%either%fast%or%slow%depending%on%whether%new%mRNA%synthesis%is%required.%neutriphil%in%acAon%slow: - changes in gene expression and synthesis of new proteins fast: - no changes in gene expression (ex: cell movement, secretion, or metabolism)3/15/15%10%Figure 16-7 Essential Cell Biology (© Garland Science 2010) Responses%can%be%either%fast%or%slow%depending%on%whether%new%mRNA%synthesis%is%required.%Figure 16-8 Essential Cell Biology (© Garland Science 2010) Two'major'types'of'signals'and'receptors:'signals'that'CAN’T'pass'the'membrane'signals'that'CAN'pass'the'membrane'cell-surface receptors: - since extracellular signal molecules are large and hydrophilic they can't cross the plasma membrane directly. So they bind to cell surface receptors -> generate 1 or more intracellular signaling molecules in the target cellintracellular receptors: - some small extracellular signal molecules pass through the target cell's plasma membrane and either activate intracellular enzymes directly or bind to intracellular receptors (that regulate gene transcription)3/15/15%11%Figure 16-10 Essential Cell Biology (© Garland Science 2010) Intracellular%receptors%%Example%1:%%Hormone%signaling%via%nuclear'hormone'receptors'(Example%2:%pages%538Q9)%Figure 16-11a Essential Cell Biology (© Garland Science 2010) Intracellular%receptors:%%Example%2:%%RelaxaAon%of%blood%vessels%via%the%gas%nitric%oxide%(NO)%Steroid hormone cortisol acts by activating a transcription regulator. - cortisol: hormone produced by adrenal glands in response to stress 1) crosses plasma membrane and binds to its receptor protein (which is located in the cytosol) 2) receptor-hormone