BIOC 212 Lecture Notes - Lecture 14: Secretion, Glycan, Galactose
29 May 2018
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3- Intracellular Trafficking
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CCV Fission
• Dynamin GTPase pinches off CCVs
o Not a member of Ras family, other GTPase family
• Dynamin monomers assemble in GTP-bound state into oligomeric rings at base of
bud
o Dynamin starts in monomeric state, bound to GTP, and forms spirals at the
base of the bud
o Wrapping around the neck of the bud
• GTP hydrolysis causes a coordinated constriction of ring that pinches off the
vesicle – fission
o When hydrolyze GTP, does so in unison in all subunits at once
o Gives the spiral a pinching effect, squeezing the bud until it pinches off from
the membrane
• Dynamin rings disassemble in GDP-bound state
o Once in the GDP-bound form, the dynamin will dissociate into monomers
again
Clathrin Uncoating
• PI-phosphatases modify PI(4,5)P2 to weaken adaptor binding
o Have PI-kinases which put the phosphate on, and PI-phosphatases that
remove the phosphate
o Removing the phosphate weakens the interaction with the adaptors (loosen)
• But still need another step to remove the coat; involves Hsp70 & co-chaperone
• Auxilin: DNAJ with clathrin-binding domain and J domain
o Co-chaperone with J domain that interacts with Hsc70 and a clathrin-binding
domain
o Binds clathrin cage when assembled onto the vesicle, activates Hsc70 --
binds on one site on clathrin
• Hsc70 binds clathrin and induces a conformational change, that disassembles
coat into triskelions
o Even though clathrin cage is not unfolded, has hydrophobic sequence that
serves as a Hsc70 binding site
o Causes clathrin to loosen and to come apart on the membrane
• Clathrin is released from Hsc70 and recycles to membrane
o Free clathrin in the cytosol recycles back to the plasma membrane so can
form a new vesicle
o Another way of using pliers
§ Not a folding step; conformational change that works in parallel to
folding
§ Special use of DNAJ co-chaperone
Traffic
• Munich subway system
• When thinking about targeting, have signal on protein that directs it to specific
compartment
o In secretory pathway, have vesicles to move proteins & lipids around
§ Need a signal to get protein into the vesicle
§ And signal on the vesicle to tell it where to go
o Two layers of targeting
o In the same way that need to get person in the subway car, and need to get
the subway car to the right location
§ Then need to let the person out of the subway car
§ Analogy to what is going on in the cell
Transport Through Golgi
• Golgi is organized into a stack of membranes is a series: cis, medial, trans
o From ER, first go to cis, then medial and trans Golgi
o From trans Golgi, go to the plasma membrane
• Old model: vesicles transport cargo between layers
o Layers are fixed; sets of vesicles going forward and other set going
backwards
o Also have vesicles going back & forth between the ER & the Golgi
• New model: each layer matures and becomes the next layer
o Golgi works like a conveyer belt
o As form this vesicular tubular cluster of vesicles coming out of the ER, it
becomes the cis Golgi, the cis becomes the medial, which in turn becomes
the trans
§ Each layer moves up as progress
§ Vesicular tubular cluster aka ER Golgi Intermediate Compartment
o The last layer (trans Golgi) breaks apart as form secretory vesicles going to
the PM or endosomes
o Cisternal maturation model
§ Each layer called cisternae
• Golgi-resident proteins are carried backwards by COP-I vesicles
o COP-I vesicle move backwards between layers of the Golgi, and between
Golgi & ER
o If have a protein that is supposed to stay in the medial Golgi, will always be
moved forward and then brought back by the COP-I vesicles
Document Summary
Not a folding step; conformational change that works in parallel to folding. Traffic: munich subway system, when thinking about targeting, have signal on protein that directs it to specific compartment. In secretory pathway, have vesicles to move proteins & lipids around. Need a signal to get protein into the vesicle. And signal on the vesicle to tell it where to go: two layers of targeting. In the same way that need to get person in the subway car, and need to get the subway car to the right location. Then need to let the person out of the subway car. Analogy to what is going on in the cell. Vesicular tubular cluster aka er golgi intermediate compartment: the last layer (trans golgi) breaks apart as form secretory vesicles going to the pm or endosomes, cisternal maturation model. Each layer called cisternae: golgi-resident proteins are carried backwards by cop-i vesicles, cop-i vesicle move backwards between layers of the golgi, and between.
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