Exam 1 will be held Friday Oct 2nd in the Tes9ng Center Arjona 110 You must sign up for an available Exam Slot on HuskyCT Exam Registra9on Link Exam slots 11 12 30 12 30 2 2 00 3 30 3 30 5 there is no regular class on exam day If you have another class con ict with the available slots you must provide a screenshot of your UConn schedule and contact me ASAP There will be 2 Review sessions before the Exam 1 Wednesday 9 30 6 8pm TLS 154 2 Thursday 10 1 6 8pm Arjona 143 Bring your Problem Sets The early exam for people with legi9mate reasons that have been cleared with me will be on Thursday 10 1 BPB 201 1 45 3 15pm Con rm with your TA aYer clearing with me If you need to take the early exam for a legiMmate reason and have NOT contacted me yet please do so ASAP david daggeR uconn edu Students who have CSD Exam 9me place accommoda9ons will be taking the exam at the CSD o ce Please get any Exam AdministraMon Forms to me ASAP MCB 2210 Exams will be taken at the Tes9ng Center Rm 110 Arjona On each scheduled Exam day there will be 3 possible Mme periods to take the exam Prior to the Exam you must follow the Exam RegistraMon link on the Husky CT site to sign up for one of the periods They will be lled rst come rst serve Exams will be taken on computer terminals at the TesMng Center You must arrive at 110 Arjona at least 10 minutes before the exam period You must have your UConn ID with you to sign in You may only bring a pen or pencil to the computer terminal and scratch paper will be provided At the start of the Exam Period you will be given a password to access the Exam via the MCB 2210 HuskyCT site The password will allow you access to the Exam only once and the exam must be completed by the end of the Exam period Signal Transduc9on How are signals transmiRed from the outside of the cell to the inside allowing cells to modify their behavior Grow or don t grow Die Kill Move or don t move Contract Turn on or o genes We ve seen that the bilayer is a barrier to physical substances it s also a barrier to many kinds of informa9on Info How are signals transmi ed across the membrane Hydrophobic signaling molecules can cross the membrane directly Steroid Hormones The receptor for this signal is in the cytoplasm or nucleus Nitric Oxide Carbon Monoxide Dissolved gas regulates many pathways Hydrophilic signaling molecules cannot cross the membrane They need to indirectly signal across the membrane by binding to the extracellular domain of transmembrane receptor proteins Types of signals Signaling via chemical messengers Autocrine paracrine and endocrine signaling Cell surface receptor binds a molecule secreted by itself autocrine a nearby cell paracrine or a distant cell endocrine Contact dependent signaling Cell surface receptor binds a signal on the surface of another cell or to extracellular matrix Basic scheme of signal transduc9on via membrane receptors The same signal can bind to mulMple types of receptor The receptor can be coupled to mulMple types of transducer Second messengers can provide a high degree of signal ampli caMon The same second messenger can be coupled to mulMple e ectors Signal 1st messenger membrane receptor transducer second messenger second messenger second messenger second messenger second messenger Effector s response grow proliferate express genes move die etc Types of plasma membrane receptors Ligand gated channels Signal opens a channel ion pore G protein coupled receptors Signal acMvates a G protein Enzyme linked receptors Signal acMvates the enzymaMc acMvity of the receptor usually a kinase G protein Coupled Receptor Signaling Transmembrane Receptor Ogen 7 membrane spanning helices Extracellular domain binds small molecule signal on the outside of the cell neurotransmiRers hormones tastants odors light Transmit signal to the cytoplasmic domain which changes conformaMon as a result TM receptor acts as a GEF Guanine NucleoMde Exchange Factor Heterotrimeric G protein Guanosine nucleo9de binding protein receives signal Three di erent subunits Two are tethered to the membrane by a covalently linked lipid Can sense the di erence in 3D shape of receptor s cytoplasmic porMon when extracellular porMon is bound vs unbound When bound they interact Transmits signal to e ector protein as a result of GTP GDP exchange G protein Coupled Receptors hRp www youtube com watch v V 0EcUr txk A really really simple example opening of K channels by acetylcholine Adenylyl cyclase a key target of G protein signaling Adenylyl cyclase G binds to adenylyl cyclase acMvaMng it This enzyme makes cAMP from ATP cAMP is an important Second Messenger cAMP binds to Protein Kinase A PKA regulatory subunit causing it to fall o The regulatory subunit blocks the kinase acMvity The regulatory subunit tethers the complex in the cytoplasm prevenMng the NLS from causing import The catalyMc subunit of the kinase is now acMve and goes to the nucleus PKA phosphorylates nuclear proteins to change gene expression Signaling via phosphoryla9on Serine Threonine Kinases Phosphorylate speci c Serine and or Threonine residues in target protein PKA PKC etc Tyrosine Kinases Phosphorylate speci c tyrosine residues RTKs Src etc Whether phosphorylaMon turns a target on or o increasing or decreasing its acMvity depends on the site of phosphorylaMon and the protein structure and is experimentally determined Adenylyl cyclase a key target of G protein signaling Signal binds a Receptor Receptor interacts with transducer the G protein G protein interacts with an e ector Adenylyl Cyclase AC produces a second messenger cAMP Second messenger interacts with e ector target PKA AcMve PKA phophorylates an e ector target CREB which results in change in gene expression The mul9ple points of signal ampli ca9on in cAMP signaling There is a growing realiza9on that signaling complexes can restrict signals in 9me and space ampli ca9on may not be everything mAKAP a sca olding protein that can form a localized complex with Protein Kinase A and Phosphodiesterase PDE In addi9on to phosphoryla9ng nuclear targets PKA phosphorylates and ac9vates PDE in response to cAMP PDE cleaves cAMP to AMP resul9ng in termina9on of signal cAMP is a common second messenger in signaling Increases in intracellular calcium are another response mediated by GPCRs PIP2 DAG Ca release in response to IP3 is a common example of second messenger signaling Calmodulin is one of the main transducers of Ca2 signals Enzyme linked receptors Signaling through enzyme linked