Documente Academic
Documente Profesional
Documente Cultură
Synaptic Siganlling
Synaptic signalling involved nerve cells releasing a signal which binds to receptors on nearby cells. This is also involved in long distance communication and uses chemicals secreted by neurons which diffuse across synaptic clefts to target cells (neurotransmitters). This type of signalling is limited to very specific areas as target cells must have receptors
Mechanisms of endocytosis
Compartmentalisation of cells and organelles obligates for a variety of transport processes to allow substances to pass between compartments and cells
Permeability of membrane
Mechanism are required to allow passage of molecules that would otherwise take place very slowly
Channel proteinsform aqueous pores allowing small inorganic ions to pass Transporter proteinsundergo conformational changed to transport molecules Active transporter proteinscouple processes/use energy (ATP hydrolysis) to drive transport Uncoupled transporteruniporter Simultaneous transfer in same directionsymporter Transport in opposite directionantiporter Exocytosisprocess by which cells release synthesised molecules and particles into the cell environmentmaintains plasma membrane integrity of the cell Transport vesicles fuse with the plasma membrane and contents are released into the extracellular space Endocytosisuptake of large molecules and particles that cannot be taken up by the cell using other meansfluids A region of the plasma membrane invaginates and forms a transport vesicle derived from contents of extracellular space
The biosynthetic secretory and endocytic pathway in cells: Anterograde processesbiosynth and delivery of proteins and lipids Retrograde processesretrieval/restoraration Endocytic processes
Coatingsform a lattice around the membrane and help shape formed vesicle: COPIretrievalretrotranslocation to Er and budding from golgi COPIIsecretory ER-Golgi anterograde transport Clathrinendocytic
Nucleation (F-BAR protein mediated) cargo selectioncoat assemblyscission (pinched off by dynamin) uncoating
Atherosclerosishardening and occlusion of arteriesno cholestrol uptake increases risk (due to polymorphism in cytoplasmic tail of LDLr)
Constituive endocytosis motifs present in cytoplasmic tails recognised by cargospecific adaptor proteins Stimulated endocytosis specific receptor-liagnd interaction allows the receptor to bind specific cargo adaptors Endocytosis is prevented until a specific signal occurs Endocytosed receptors are returned to the PM via exocytosis
Early and late endosomes have different protein compositions: Acidification of environment as the endosome maturesfavours degradation of content Hydrolytic enzymes only become fully active in endolysosomes
When resistant or slowly digestible molecules remian the endolysosome will become a lysosome Lysosomes40 hydrolytic enzymes (acid hydrolasesH+ pump maintains 4.5-5 pH) which is the principle site of intracellular digestion
Macropinocytosis fluid uptakeall cells do thisruffled extensions of the PM form around a region of extracellular fluid and internalise whole regionvesicle fuses with early endosomes
Caveolin-mediated endocytosiscaveolinsPM patches rich in glycophospholipids and certain glycoproteinstake up diverse molecules such as vits, bacteria, viruses, proteins, lipids, proteinsrequires dyamin for scissionas they are semi-transmembrane proteins they are not removed from caveolae vesicles unlike clathrin which detaches Clathrin and caveolin independent endocytocisno clathrin, caveolinscan be dyamin (scission) dependent or independent
Transcytosis combination of endocytosis and exocytosiscell encloses material to form a vesicle in apical surface e.g. Ig from mothers milk
Polaristaion of cells
Many cells are inherently polarisedrequired for function e.g. apical-basolateral organisation in epithelial cells Apical and basolateral systems utilise separate early endosome compartmentscargo may contain recycling or transcytosis signals and will proceed to these routes if absent transfer into joined late endosome and digested
The recycling of endosomes can serve as a reservoir from important PM receptors e.g. GLUTs in muscle/fat cells
Exocytosis:
Targetingdockingfusion and release Regulated secretory pathwaysoccurs in endocrine, exocrine and neuronal cellsspecialised secretory vesicle compartmentse.g. histamine secretion in mast cells, insulin secretion in pancreatic beta cells, adrenaline in adrenal chromaffin cells SNARE proteins facilitate membrane fusion reactions V (monomer) and T (trimer) SNARE complementary pairing provides specificity for docking
Synaptic vesicles located in active zonevesicles fuse with PM and release NTpostsynaptic cell membrane contain receptors and enzymes to degrade NTs
Peptide NTssynthesised in cell body of neuronpackaged into vesicles through golgi vesicles moved along microtubule tracks driven by ATP motor proteins (fast `400mm/day)
Clostridial Neurotoxins:
Tetanus paralysis, fatal respitory/heart failure Botulismparalysis, impaired respiration, autonomic functions After entering circulation, CNs bind very specifically to the presynaptic membrane of motorneuron nerve endings Different toxins can affect different neurons but results the same block presynaptically causing electrical silenceinhibition of exocytosis of NTs e.g. acetylcholine