intracellular protein trafficking Flashcards
what is protein targeting/sorting
mechanism by which proteins are transported to their appropriate destinations in the cell or outside it
when does the first step of protein sorting take place
while translation is still taking place
where are proteins destined for the ER, Golgi apparatus, lysosomes, plasma membrane synthesized on
ribosomes that are bound to the ER membrane
where are proteins destined for the nucleus, mitochondria, chloroplast and peroxisome synthesized on
free (non-bound) ribosomes
when can proteins be translated to the ER (2)
- during their synthesis on membrane-bound ribosomes (co-translational translocation)
- After their translation have been completed on free ribosomes in the cytosol (post-translational translocation)
what is the first step of the Co-translational pathway
association of ribosomes with ER
what is the specific aa (amino acid) sequence that target ribosomes for binding to the ER membrane
signal sequence at the amino (N) terminus of polypeptide
what removes the signal sequences
proteolytic cleavage.
what binds to the ribosome and signal sequence, prevents further translation and targets the complex to the ER
signal recognition particle (SRP)
what does signal recognition particle (SRP) contain
six polypeptides and a small cytoplasmic RNA (srpRNA)
after translation inhibition, what does the complex bind to 1
SRP receptor on the ER membrane
after the SRP is released what does the ribosome bind to
translocon
what is the translocon a complex of
three transmembrane proteins called Sec61
what does cleavage of the signal sequence by signal peptidase release
polypeptide into the lumen of the ER
what maintains the unfolded conformation of the proteins
cytosolic chaperones
during post-translational import, what recognizes the signal sequences
Sec62/63 complex
what does Sec63 protein associate with
chaperone protein (BiP)
what is the function of chaperone protein (BiP)
acts as a molecular ratchet to drive protein translocation into the ER
what happens to proteins destined for secretion from the cell or residence within the lumen of ER, Golgi, or lysosome
(i) released into the lumen of ER
(ii) translocated across the ER membrane
what are the two ways in which insertion occurs
(1) with a cleavable signal sequence and a single stop-transfer sequence
(2) with an internal non-cleavable signal sequence
what are the N and C terminus of membrane proteins
amino (N) or carboxy (C) terminus
in the first type of insertion, what happens when the polypeptide chain crosses the membrane
signal sequence is cleaved and amino terminus of the polypeptide chain is exposed in the ER lumen
what halts translocation in the ER membrane, for the first type of insertion
stop transfer sequence
in the second type of insertion what does the signal sequence act as
anchors the protein in the membrane with its C terminus or N terminus in the ER lumen
what determines whether C-terminus or the N-terminus is in the cytosol
orientation of the polypeptide chain
how does Insertion of a protein that spans the membrane multiple times occur
after the signal sequence by repeatedly stopping the sequence
ER is the site of
protein folding assembly of multisubunit proteins, disulfide bond formation, the initial stages of glycosylation, the addition of glycolipid anchors to some plasma membrane proteins
what assists in the 3D folding of polypeptides in the ER
Hsp70 chaperone (BiP)
what is the function of
a) cytosolic chaperones
b) Mitochondrial chaperones
a) stabilize the un-folded configuration
b) facilitate transport and subsequent folding of the polypeptide chain within the organelle
what happens to proteins that travel along the secretory
pathway in transport vesicles
they bud from the membrane of one organelle and then fuse with the membrane of another
what are transmembrane proteins that enter the transitional ER marked with
sequences that signal either their export from or retention within the ER
what are the export signal sequences
- di-acidic (eg., Asp-Asp or Glu-Glu)
* Di-hydrophobic (eg., Met-Met)
what are proteins destined to remain in the ER lumen marked by
sequence Lys-Asp-Glu-Leu (KDEL). they exported from ER to Golgi, and are recognized by a receptor in the ERGIC and are transported back to the ER
where does protein modification occur in the Golgi
at its medial and trans Golgi stacks
what are proteins transported through after being processed in the Golgi
through the secretory pathway which involves aorting of proteins into different kinds of transport vesicles which bud from the trans Golgi network and deliver their contents to appropriate locations
what are the types of coated vesicles
COP-coated vesicles (COP1 and COP II)
Clathrin-coated vesicles
what vesicles carry secretory proteins from the ERGI or Golgi, budding from the transitional ER and carrying their cargo forward along the secretory pathway
COPII coated vesicles
describe the function of COP1 coated vesicles
bud from the ERGIS or Golgi. It is the coat protein on vesicles moving from one Golgi cisternae to another during secretion and on the retrieval vesicles that return resident ER proteins marked with KDEL signals
what are Clathrin coated vesicles responsible for
uptake of extracellular molecules from the plasma membrane by endocytosis and transport of molecules from the trans Golgi network to endosomes, lysosomes or the plasma membrane
