Endocytosis and Exocytosis

Cell to cell communication Endocrine Signalling

Cell to cell communication can occur through hormones released from a cell which affect another cell/s throughout the body. This is important in long distance communication and maintaining homeostasis. Transmission occurs via the circulatory system.

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

Some clathrin-mediated endocytoisis is badviruses e.g. rubella

Mechanism of clathrin assembly

Nucleation (F-BAR protein mediated) cargo selectioncoat assemblyscission (pinched off by dynamin) uncoating

Clathrin-mediated endocytosischolestrol uptake

Atherosclerosishardening and occlusion of arteriesno cholestrol uptake increases risk (due to polymorphism in cytoplasmic tail of LDLr)

Clathrin-mediated endocytosisiron uptake

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

Different types of endocytosis Cathrin-mediated endocytosis

Phagocytosisuptake of large particle membrane folds around the object and the object is sealed off into a large vacuole known as a phagosomeusually undertaken by phagocytes (neutrophils, macrophages, moncytes etc) but every cell has the capabiltytriggered by eat me siganlsphagosome fuses with lysosome to form phagolysosomethe usable content is released in cell, unusable outside cell

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

Basic processes in synaptic transmission:

Action potentialvoltage gate Ca channels openCa influx triggers exocytosisNT is releasedresponse in post-synaptic neurontermination by removal of NT from synaptic cleft by enzyme degradation/reuptake into presynaptic terminalNT loss via diffusion Neuroransmitter axons can be 1mm to 1m long therefore NTs must travel long distances between site of synth and site of secretion Small NTs enzymes that synth NT transported to pre-synaptic terminals (slow ~5MM/DAY) synth of NT occurs in pre-synaptic terminal then packaged into SVs (precursors imported into terminal)

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