BIO230H1 Lecture Notes - Lecture 1: Secretion, Cleavage Furrow, Epithelial Polarity
BIO Lecture -
Membrane trafficking
Cells engage the extracellular space
• Communication with other cells
• Acquire resource
Need control and dynamic changes to the plasma membrane: cells are polarized e.g.
epithelial cells and nerve cell: different plasma membrane domains → different
proteins at different side → different functions
• Apical side of epithelial cell: face lumen
Polarized trafficking routes: start and destination
• Secretory pathway: ER → Golgi → secretory vesicle → plasma membrane
• Endocytic pathway: plasma membrane → early endosome → late
endosome Golgi send enzymes / Golgi → lysosome / Golgi
Sorting stations: vesicles and proteins sorted to different compartments
• Early endosome for endocytic
• Cis and trans Golgi networks: for secretory pathway
Retrieval mechanisms and general balance among routes
• )nside the cell: between ER, Golgi, endosome
Secretory pathways
• Constitutive: not regulated, operates continuously
o Required in all cells
o Soluble protein, membrane lipids, membrane proteins
• Regulated: requires signal hormone, neurotransmitters
o Function in specialized cells endocrine, neurons
o Soluble proteins and other substances
o Stored in secretory vesicles, released upon signals extracellular
signal → intracellular signaling pathways
o E.g. Mast cell release stored histamine after induction by a soluble
extracellular stimulant
o Provide extra plasma membrane when needed
▪ Cleavage furrow newly formed cells need plasma
membrane: phospholipids from endosome
▪ Phagocytosis engulfing: phospholipids from endosome
▪ Wound repair: phospholipids from lysosome
• )n both pathways, to make a mature vesicle:
o Golgi components retrieval: e.g. recycling clathrin coat
o Cargosecretory proteins are sent to the secretory vesicles for
multiple times: the vesicle gets concentrated
find more resources at oneclass.com
find more resources at oneclass.com
• After the vesicle is mature: docking plasma membrane → fuse → release
Endocytic pathways: counterbalancing secretory
• )nvagination → fission
• Destination of endocytic vesicles after joining early endosome
o Recycling: sent back to where it comes from
o Transcytosis: go to the other side of the cell basal → apical ; apical
→ basal
o Degradation: go to lysosome
• Cell collect resources by endocytosis e.g. cholesterol
Make transmembrane LDL receptor
→ Cholesterol – LDL
→ LDL – LDL receptor
→ Coat proteins coated pit selecting cargo adaptor protein bind
to endocytosis signal in cytoplasmic tail of LDL receptor, recruiting
clathrin
→ endocytosis and uncoating
→ fusion with early endosome
→. LDL receptor recycled back to the same plasma membrane
budding from tubules – mainly membrane protein
. cargo go to lysosome budding from main parts full of soluble
protein → LDL degradation and release of free cholesterol
• phagocytosis: internalize pathogens
o phagocytic white blood cell: use pseudopod伪足 to engulf
bacterium
Local changes during trafficking
membrane change:
molecular machinery is in the cytosol, different for the changes
• fusion: exocytic vesicles fuse with plasma membrane
o cytosol → extracellular
o SNARE proteins a large family of TM proteins: specify membrane
to fuse and conduct the process – forming four-helix bundle,
pulling membranes together and squeezing out water for
membranes to fuse
▪ V-SNARE: vesicle
helical domain
▪ T-SNARE: target membrane
helical domains
• invagination: endocytic vesicles invaginating in
o extracellular → extracellular
o receptor-mediated: Clathrin drive this event
▪ inner layer: adaptor – types, selecting cargo receptor
▪ outer layer: clathrin triskelions – heavy chain + light
chain → giving curvature, determining geometry of the
find more resources at oneclass.com
find more resources at oneclass.com
vesicle
o COP) and COP)) also drive this event
o Dynamin: drives fission after vesicle invagination
▪ Dynamin GTPase and associated proteins scission of
newly formed vesicles from the membrane: spiral around
the neck
▪ Mutation of dynamin → cannot perform fission
• budding: form a vesicle and gocommon for virus
o cytosol → extracellularvesicle go together with cargos
o multi-vesicular body: formed during endosome maturation,
contain intraluminal vesicles
o ESCRT complex drive this event
▪ ESCRT-: bind to ubiquitin multi-ubiquitin tag on cytosolic
domain of membrane proteins, P)P is an additional
docking site
▪ ESCRT-O transfer the protein to ESCRT-), then to ))
▪ ESCRT-))) form a large complex → bend the membrane
▪ ESCRT complex push the cargo into the budding site
o For virus budding: topologically equivalent to internal budding
from endosome membrane, the destination is outside of the cell
instead of multi-vesicular body inside endosome
Organization of trafficking
Cargo regulation
• Signal sequence / moieties
Transport machinery
• Signaling lipids P)Ps – phosphatidylinositol phosphates
o Different organelles → different sets of P)/P)P kinases and
phosphatases → different distribution of P)Ps among organelles,
or among different domains of a continuous membrane →
different proteins recognize different sugar head groups
phosphorylation patterns → directing vesicles to different
locations or cause the membrane to do different things
o P) ⇄ P)P / P)P
o P) ⇄ P)P
o P)P → P),P → P)P
o P)P ⇆ PI(4,5)P2 ⇆ PI(4)P / PI(3,4,5)P3 ⇆ PI(3,4)P2 ⇆ P)P
o you don’t have every combination of pathways, you can only add
or remove one phosphate each time
• Small GTPase
o GEF: guanine-nucleotide-exchange factor: GDP → GTP
▪ Sometimes just take off GDP, sometimes add GTP → depend
on specific GEF in specific environments
o GAP: GTPase-activating proteins: help GTP hydrolysis
o GTP-bound = active
find more resources at oneclass.com
find more resources at oneclass.com
42
BIO230H1 Full Course Notes
Verified Note
42 documents
Document Summary
Cells engage the extracellular space: communication with other cells, acquire resource. Need control and dynamic changes to the plasma membrane: cells are polarized (cid:523)e. g. epithelial cells and nerve cell(cid:524): different plasma membrane domains different proteins at different side different functions: apical side of epithelial cell: face lumen. Polarized trafficking routes: start and destination: secretory pathway: er golgi secretory vesicle plasma membrane, endocytic pathway: plasma membrane early endosome late endosome (cid:523)golgi send enzymes(cid:524) / golgi lysosome / golgi. Sorting stations: vesicles and proteins sorted to different compartments: early endosome for endocytic, cis and trans golgi networks: for secretory pathway. )nvagination fission: destination of endocytic vesicles after joining early endosome, recycling: sent back to where it comes from, transcytosis: go to the other side of the cell (cid:523)basal apical ; apical. Basal(cid:524: degradation: go to lysosome, cell collect resources by endocytosis (cid:523)e. g. cholesterol(cid:524)
