Membrane Proteins and the Secretory Pathway Flashcards
four types of membrane proteins
transmembrane, monolayer-associated, lipid-linked, protein-attached
Type I topology
single pass protein anchroed to the lipid membrane with a stop transfer anchro sequence, have their N-terminus targeted to the ER lumen
Type II topology
single pass protein anchored with a single-anchor sequence and hte carboxyl terminus in the ER lumen
Type III topology
single pass protein with a signal-anchor sequence and the amino terminus in the ER lumen
Type IV topology
multi-pass protein, amino terminus on either side
glycosylphosphatidylinositol (GPI) anchor
modified lipid in cell membrane that cells adhere to
some type I proteins exchange their carboxyl terminal transmembrane segment for a GPI anchor
Describe the directions of vesicular traffic in cells.
protein transport into ER
signal recognition particle (SRP) recognizes signal sequence and brings it to receptor in the ER membrane
protein goes through channel, and signal is eventually cleaved by a signal peptidase
What are some different ways to orient proteins based on signal sequence?
N-linked glycosylation
the process of adding sugar molecules onto all proteins in the ER membrane, same sugars
important for protein stability
BiP
one of many ATP-dependent chaperones that assist folding as the protien emerges from the translocon
Calnexin
calcium binding protein that monitors that folding of glycoproteins
binds to oligosaccharides and “senses” when the protein is correctly folded
mannosidases
trim mannose residues from the oligosaccharide, function similarly to calnexin to ensure proper folding
protein disulfide isomerases (PDIs)
catalyze formation of disulfide bonds
ERP57
chaperone protein that works with calnexin to ensure proper folding of proteins using the trimming of the oligosaccharides as a guide
SEL1
protein in the ER that pushes improperly folded proteins out as a single chain, which is then polyubiquitinylated and degraded
PERK
protein kinase that phosphorylates eIF2alpha, which blocks translation
ATF4 can escape the transtion block so it goes to the nucleus and activates a stress response
ATF6
released from the ER membrane by high levels of BiP, and goes through the golgi to get cleaved and become a transcription factor to activate stress genes
IRE1
BiP interaction activates a unique splicing mechanism, causes intron mechanism for XBP1 to be inactivated, creating a transcription factor to activate a stress response
also responsible for triggering autophagy or apoptosis through activation of Jun Kinase
unfolded protein response
a collection of several mechanisms the cell can undergo to deal with unfolded proteins
uses BiP as a sensor
ER-associated degradation (ERAD)
a process of degradation that proteins undergo if proteins cannot fold properly or take too long to fold in the ER, uses SEL1 to unfold proteins and mark for degradation
functions of the cis golgi network
sorting, phosphorylation of oligosaccharides on lysosomal proteins
functions of the cis cisterna of golgi
removal of mannose
function of mdial cisterna of golgi
removal of mannose and addition of N-acetyl-glucose (GlcNac)
trans cisterna
addition of galactose and NANA
trans golgi network
sulfation of tyrosines and carbohydrates, prepare for vesicular transport
Describe the vesicular transport from the Golgi.
packaging of cargo in the Golgi
need coat complex II (COPII)
recruitment of cargo proteins and coat machinery
formation of vesicle that pinches off
vesicle compartment topology
lumenal aspect of the ER correlates to the outside of the cell once the transport completes
recycling of components
uses coat complex COPI and peptide sequences often have a KDEL motif that directs ER proteins form the GOlgi to recyling
mannose-6-phosphate receptors
integral membrane proteins that bind lumenal lysosomal hydrolases, causes formation of clathrin coated vesicles
marked for transport to early or late endosomes, which become lysosomes
exosomes
small vesicles released from the plasma membrane
have roles in coagulation, intercellular signaling, and waste management
generated in multivesicular endosomes
can possible shuttle ncRNAs to other cells for signaling and regulation
three types of endocytosis
phagocytosis, pinocytosis, receptor-mediated endocytosis
pinocytosis
ingestion of small bits of the plasma membrane with extracellular fluid
small vesicles c alled caveolae
phagocytosis
ingestion of large parthicles and delivery to lysosomes
requires the actin cytoskeleton
receptor-mediated endocytosis
responsible for uptake of essential nutrients such as iron and cholesterol
used to recycle and down-regulate receptors
uses clathrin coat and adaptin molecules along with the specific receptors
endosomes
come from endocytosed vesicles that fuse with each other, early and late endosomes, eventually becomes lysosomes and contents are degraded
two types of autophagy
microautophagy and macroautophagy
operates to recycle cellular components, active under startvation conditions
microautophagy
occurs by the capture of small volumes of cytoplasm by invagination of the membranes in multivesicular bodies and lysosomes
cytoplasmic components are hydrolyzed within the lysosomes
macroautophagy
involves the engulfment of large volumes of cytoplasm including glycogen granules, ribosomes, and organelles
autophagic vacuole
forms when flattened sheets of membranes derived from the smooth ER coalesce to form a double membrane vesicle
fusion with lysosomes forms an autolysosome, where engulfed contents are degraded
two types of secretion
constitutive secretion - simply move materials out of the cell in regular intervals, both soluble and membrane associated proteins
regulated membrane fusion - take secretory vesicles and accumulate them near the plasma membrane, only allow them to fuse with the plasma membrane when stimulated with a signal, electrical activity, etc.
three fates of internalized receptors
recycled, degraded, transcytosed
Descrube the sorting of proteins from the trans golgi network to the lysosome.
indirect and direct pathways
indirect goes from golgi to membrane, which can then be engulfed and degraded
direct goes to late endosome and then lysosome or goes directly to lysosome
Describe the composition of the lysosome.
sorting of plasma membrane proteins in polarized cells
direct sorting - goes from Golgi to the right surface of the cell
indirect sorting - goes from golgi to basolateral surface and then sorted from there through early endosomes
