Cell Biology of Neuron and Glia PDF

#separator:tab #html:true Wat is het soma/cellichaam? "Waar eiwitten worden gemaakt om door het axon en de dendrieten te worden getransporteerd." Wat is het receptieve gedeelte van een neuron? De dendrieten Wat is het ganglion? De verzameling cellichamen buiten het CZS. Wat is een dendriet? "Ontvang...

#separator:tab #html:true Wat is het soma/cellichaam? "Waar eiwitten worden gemaakt om door het axon en de dendrieten te worden getransporteerd." Wat is het receptieve gedeelte van een neuron? De dendrieten Wat is het ganglion? De verzameling cellichamen buiten het CZS. Wat is een dendriet? "Ontvangt input van vele andere neuronen en dragen die signalen naar het cellichaam.Functie: informatie verzamelen door synaptische input.Groot gedeelte van neuron: <99% van neuron membraan.Dendriet kan informatie ontvangen van 200.000 synaptische inputs." Wat is een axon? "Functie: informatie doorgeven aan verschillende neuronen, spieren en klieren." Wat is de nucleus? De verzameling cellichamen binnen het CZS. Wat is de axon hillock (axonheuvel)? "Plaats in het neuron waar het actiepotentiaal begint.GO of No GO. Beslispunt wel/niet doorgeven signaal binnen neuron.Somt het totale aantal ontvangen signalen op, zowel remmende als prikkelende signalen.Als deze som de drempelwaarde overschrijdt, wordt het actiepotentiaal geactiveerd." Hoe is een neuron opgebouwd? "Functionele eenheid zenuwstelsel.Input: dendrites (haalt signaal op en geeft dit door).Output: axons (einde neuron, stuurt het signaal uit).Axonen omgeven door myelin sheath.In het soma (cellichaam) vindt eiwitsynthese plaats.In axon hillock: GO of No GO. Beslispunt wel/niet doorgeven signaal binnen neuron.Neuronen kunnen contact maken met elkaar of met weefsels bijv. spieren." What is a neuron? "86 billion neurons with 1 x 1015 synapses.Post-mitotic: doesn't divide.Highly polarised: long axons and multiple shorter dendrites, many synapses. Oriented towards one direction.Highly compartmentalised: certain organelles are only found at certain locations.Transmit, receive and process signals at distant locations (synapses).Long lifespan (neurons stay with you your whole life) --> tight control and strong support needed.Very long." What challenges do neurons face? "How to get to the right place in the brain.With whom to make contact.How to generate and maintain polarization.How to supply distant synapses with proteins and lipids.How to maintain energy levels in distant synapses.How to respond to changes in local environment and activity. " What is a synapse? "The place where communication between neurons takes place. The information processing and transmission node.Synaptic vesicles come from an axon and should not go into dendrites but into the axon. These vesicles fuse at the presynaptic terminal at the position of the active zone." What does synapse function require? It requires energy, proteins and lipids. What is an active zone? "A dense structure where the vesicles can fuse on the presynapse.Where voltage gated Ca2+ channels and clusters of proteins that make sure Syt-1 is close to the Ca2+ channels are located.AP opens Ca2+ channels --> influx Ca2+ --> fusion of vesicles.Proteins bring the vesicles in close proximity to Ca2+ channels (priming and docking).Syt-1 binds Ca2+ but has a low affinity for Ca2+ --> vesicles pulled to membrane --> fusion.Postsynaptic receptors are perfectly aligned at the places where vesicles fuse." What is the postsynaptic density? "Where the receptors are located on the postsynaptic cell." What is the axon initial segment (AIS)? "Place where APs are generated.Cellular membrane domain near proximal end of axon.Contains a concentrated cluster of sodium and potassium channels that are estimated to be much higher than in other membrane domains, based on intensity of immunostaining.Acts as a barrier for proteins that have to go into dendrite and not into axon --> makes sure neurons are polarized and stay polarized.If no axon initial segment --> proteins that should be in postsynapse will be in presynapse." What is a neuromuscular junction (NMJ)? "Has many organelles and mitochondria.Two active zones (in brain synapses normally one) --> high release probability --> more vesicles can fuse and be released for a longer time." What is a zip-code? Sequences of nucleotides, aka RNA “ZIP codes,” are recognized by proteins that act like mail carriers and deliver the RNAs to where they are supposed to go. What are the major organelles required for neurons and synapse function? "The same organelles that are found in mitotic cells.sER: creation/storage of lipids and steroids.rER: synthesis of various proteins.Golgi: posttranslational modifications, e.g. glycosylation and sorting for transport." How does the intracellular transport pathway through the ER and Golgi work? "mRNA leaves nuclear envelope --> translation --> migration to ER.Formation transmembrane proteins in ER --> vesicles leave via ER exit sites --> ER Golgi intermediate complex (ERGIC): cargo still goes both ways --> proteins mature a bit in Golgi and posttranslational modifications proteins --> vesicles sorted in transgolgi network (TGN) --> cargo goes back to ER or goes towards PM for secretion --> vesicles further mature on their way to PM --> vesicles contain SNARE proteins needed to fuse with membrane.This was believed until 10 years ago." How are organelles organized in neurons? "ER: mostly everywhere in neuron.ERGIC: more spotty because the structure is more vesicle-like.GA: only present in cell body, sometimes in dendrites. Not present in axons.Recycling endosome (RE): present throughout whole cell. " What is the organization of the ER inside a neuron? "Secretory organelle.Continuous dynamic network in soma, dendrites and axon --> direct communication possible.Present in pre- and postsynaptic terminals.Allows local protein translation --> no need to make it in cell body and transport to other far away location.Major calcium store.Major lipid source.Distributed all over cell, but mostly in cell body.sER: creation/storage of lipids and steroids.rER: synthesis of various proteins." What contact does the ER make and what is it needed for? "ER makes contact with all organelles via ER membrane contact sites --> all organelles are interconnected.ER is a strong regulator of other oranelles.Lipid transfer (between ER and lysozomes).Calcium exchange: ER supplies Ca2+ to mitochondria to make ATP via contact sites. ER causes local differences in Ca2+ concentrations --> synapses with cell.Interactions are dynamic." How do ER-PM contact sites function in calcium homeostasis and axon growth? "Contact sites with PM supply membrane with plasma lipids and get more Ca2+ into ER.Presynaptic terminal: Ca2+ comes in from PM and Ca2+ release from ER (stays longer) (important for vesicles like lysozomes which need prolonged Ca2+ release to fuse)." What is the organization of the Golgi inside neurons? "Secretory organelle.Mainly present in soma (GOs in some dendrites).Main organelle for post translation modifications (e.g. glycosylation).Main organelle for sorting cargo.Three subzones: cis (GM130), medial (ManII), and trans (TGN38). " What is the organization of ERGIC in neurons? "=ER-Golgi intermediate complex.Secretory organelle.Compartment between ER and Golgi.Receives COPII-coated vesicles from ER --> vesicles go to Golgi.Receives COPI-coated vesicles from Golgi --> go to ER.Role in folding and quality control nascent proteins.Role in glycosylation of proteins.If protein is misfolded --> protein goes back to compartment. " Why are Golgi-dependent and Golgi-independent secretory routes in dendrites important? "Because they show evidence for local translation of mRNA." "Can we make fully glycosylated proteins in the axon?" "Recycling endosomes can take over function of Golgi: locally translated proteins like transmembrane proteins act without Golgi --> no glycosylation." "How does the neuron transport locally made membrane proteins?" "Transmembrane proteins require a vesicle to be transported to the PM." What is the RUSH system? "= Retention Using Selective Hooks.Used to synchronize secretory protein trafficking.Visualizes transport of fluorescent protein from ER through Golgi to PM.Based on Streptavidin-Biotin interaction.Hook: a protein localized to ER or Golgi tagged with streptavidin. Any organelle can be targeted.Reporter: a protein of interest (X) tagged with streptavidin-binding peptide (SBP).Streptavidin (protein) binds to SBP-X --> biotin added to complex --> SBP-X released from complex --> SBP-X can travel away from ER (allows time in secretory pathway).KDEL motive makes sure proteins stays in ER.Protein of interest (NPY) bound to fluorescent protein and SBP.Proteins are released all at one --> easy to follow.Ex. RUSH used in study of neurodegenerative diseases. How are different proteins affected or how do they affect ER-Golgi traffic." How can secretory cargo trafficking in neurons be tracked? "Both pictures same conditions. Left: diffuse signal. If biotin is added --> GFP is released from hook in ER and travels to Golgi." How much energy does the brain consume? "± 20% of the energy budget --> many mitochondria needed." Which processes in the brain are energy demanding? "Maintaining ion gradientTransportSynapse assembly/maintenanceSV refilling and recyclingCalcium homeostasis" How is ATP generated at presynaptic terminals? "Glucose main energy source to generate ATP.Synapses consume ± 55% of neuronal ATP.Glycolysis is fast but inefficient (doesn't make much ATP) --> mitochondria needed.Pyruvates are transported to mitochondria where a lot of ATP is made.Astrocytes are important for regulating metabolism. " How is ATP consumed at presynaptic terminals? "Lot of ion exchange and recycling --> lot of protein and organelle degradation." In which ways can more mitochondria be attracted to the neuron? "If synapse is active and requires a lot of energy it attracts and recruits mitochondria to pre- and post-synaptic sites. Remodelling of mitochondria (influenced by calcium signalling) attracts more mitochondria to presynaptic terminal (essential for energy).Glutamate transporters are dynamic and are recruited to synapses which provide a higher income of glucose." Which degradative pathways are there? "Autophagy:Proteostasis is essential for neuronal survival.To get rid of organelles (or big clusters of proteins) by engulfing them --> degradation in lysosomes.Endosome becomes more acidic as it goes from early endosome to late endosome and lysosome. Lysosome is very acidic.Membrane formed --> autophagosome --> fusion with lysosome --> autolysosome.Recycling of receptor can happen at multiple stages of endosome maturation.Endolysososmal pathway:Lysosomes are terminal degradation hubs.Mainly for proteins.Local endocytosis that doesn't lead to degradation, e.g. refilling of SV with NT.Used by microglia." What evidence is there for lysosomes being important for neurons? There are juvenile brain diseases in which lysosome production doesn't work properly. What proteins do early and late endosomes have on their membrane? Early and late endosomes have different Rab proteins expressed on their membrane. What is autophagy? "Degrades dysfunctional organelles and protein aggregates.A way of recycling the cell’s own genetic material by using lysosomal hydrolytic enzymes.A damaged organelle or small amount of cytosol becomes surrounded by a double membrane --> lysosome fuses with outer membrane of vesicle --> lysosomal enzymes dismantle the inner membrane and the enclosed material --> small organic compounds are released to cytosol for reuse." What are the different forms of autophagy? "Bulk autophagyAggrephagy: protein aggregates are taken up.ERphagy: small part of ER can be selectively eaten by autophagy system.Mitophagy: part of mitochondria taken up by autophagy. Not whole mitochondrium is eaten up. " What might happen if there is no autophagy? No autophagy --> synapse might function better: more ER, more Ca2+, more APs. What type of ER is found in dendrites? Dendrites and cell bodies contain both rER and sER. What type of ER is found in axons? Axons contain only sER.