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Endosomes
Vesicle-bound materials are transported to a dynamic network of tubules and vesicles known collectively as _______
H+ ATPase
The fluid in the lumen of endosomes is acidified by a _______ in the membrane
Early Endosomes
Typically near the periphery of the cell; one of the classes of Endosomes
Late Endosomes
Typically further from the cell membrane; one of the classes of endosomes
Decrease; Rab; internal
Early endosomes progressively mature into late endosomes by the sequential _____ in pH, exchange of ____ GTPases, and a major change in the ______ morphology of the structures
Housekeeping receptors
Receptors responsible for the uptake of materials that will be used by the cell; we use on a day-to-day maintenance
Low
Housekeeping receptors dissociate in the ____ pH environment of the early sorting endosome and are recycled
ESCRT complexes
The vesiculation process of signaling receptors is orchestrated by a series of protein complexes known as ______
Multivesicular body (MVB)
Internal vesicles in the late endosome, cause it to be referred to as ______
Early endoscopes
The primary sorting compartment for internalized material
High; low
Early endosomes have a ____ surface to ___ volume ratio to allow for the accumulation of membrane components heading back to the PM
Microdomains
Specialized domains orchestrate membrane tabulation, invagination, and fusion by creating _____ within the same endosome
V; rotary; protons(H+);
__-type _____ ATPases pump _____ into the endosomes, progressively lowering the luminal pH along the endocytic pathway
pH
The _____ gradient controls where each cargo molecule dissociates
Transmembrane; late
MVBs form when sequestered _______ proteins get aggregated into membrane invaginations of the _____ endosome
Endosomal
MVBs pinch off and form small vesicles inside of the ______ lumen
Plasma membrane; exosomes
In some cells, the MVB may fuse with the ____ _____, releasing _____ into the extracellular fluid
Clathrin-mediated
The endosomal pathway is largely used by vesicles formed by ________ endocytosis
Trans Golgi Network (TGN)
Nonclathrin/noncaveolar endocytic structures deliver components to the _______
ER export sites (ERES)
Transport of newly synthesized proteins out of the ER takes place in specialized areas called _________
Vesicular Tubular Carriers (VTCs)
Vesicles and tubules detach from the ER and move to the Golgi as transport intermediates called _____
3 modes of transport out of the ER used by cargo molecules
Bulk flow(soluble luminal proteins); signal-mediated transport (via COPII); partitioning in the lipid bilayer
Sar1 GTPases
_____ initiates the formation of the ERES by assembling COPII coats that form coated buds and concentrate integral membrane proteins in the bud
SNARE
The _____ proteins allow vesicles and membrane tubules that bud from the ERES to fuse themselves to form a tubule cluster
Rab1 and Arf1
____ and ____ effectors help link newly formed vesicles to the cytoskeleton
Dynein
Molecular motor ___ helps detach VTCs and transports them to the Golgi
Cis-Golgi
VTCs fuse with membranes on the tubular __-Golgi network, releasing cargo proteins and lipids Into the Golgi
Carbohydrate
Function within the secretory membrane system: is a factory to synthesize the _______ chains of glycoproteins, proteoglycans, and polysaccharides
Protein
Function within the secretory membrane system: A ______-sorting station for delivery to many cellular destinations
Sphingomyelin
Function within the secretory membrane system: It synthesizes _______ and glycosphingolipids; these lipids associate with cholesterol and influence sorting
Microtubule Organizing Center (MTOC)
Ribbon-like structure adjacent to the nucleus and close to the centrosome
Cisternae
Golgi consists of flattened stacks of membrane ______ interconnected by a network of tubules and vesicles at the rims of the stacks
Microtubule
The stacks of Golgi are anchored to the ______ network that emanates from the MTOC
3 proposed mechanisms to explain transport of cargo through the Golgi
Vesicle transport, cisternal progression, and lipid partitioning mechanism
Golgi; cytosolic
Peripheral proteins (like GTPases and COPs) exchange constantly between the _____ membranes and _____ pools
Glycosyltransferases
Golgi enzymes that adds carbohydrates to a chain
Glycosidases
Golgi enzymes that takes off carbohydrates from a chain
Serines and threonines; glycosylation
Oligosaccharides can also be added to ____ and ____ in O-linked _______ to generate proteoglycans
Prohormone convertases
Some proteins, including peptide hormones made as large precursors, are cleaved into active fragments in the Golgi by ______ _______ (proteases)
Trans-Golgi network (TGN)
The exit pathway from the Golgi system; a system of vesicles and tubules similar to the VTC of the ER
Cell; lysosome; secretory
Cargoes that arrive at the TGN are destined for one of three places: the ____ membrane, endosome/______, or _____ granules
Kinesin
Vesicles are carried by _____ along microtubules to the plasma membrane from the TGN
Apical and basolateral; tight
Epithelia have functionally and compositionally distinct ____ and _____ membranes separated by ____ junctions that prevent diffusion btw the two membrane divisions
Carrier
Mechanism for polarized sorting of membrane components: selective packaging of proteins destined for each into distinct ____ vesicles at the TGN
Basolateral
_____ targeting inlvoes sorting signals in the cytoplasmic domain that contain YXXØ and [DE]XXXL[LI] motifs
Apical; lipid rafts
_____ targeting may involve partitioning into ____ ____ enriched with sphingomyelin and cholesterol formed in the TGN
AP and BL
Mechanism for polarized sorting of membrane components: Random distribution to the ___ and ___ membranes, followed by their selective retention and depletion, concentrating them in one place
Nonpolarized; polarized
Uniformly distributed proteins that preexisting on a ______ cell will redistribute in a _____ fashion in response to cell-cell contacts that initiate polarization
GPI; transcytosis
Proteins that associate with lipid rafts, including ____-anchored proteins, use _____ to reach the apical domain
Golgi
As the endosome mature and acidify, proteins are dissociated from MPRs and the MPR is recycled to the ____
LAMP (lysosomal-associated membrane proteins)
_____ family use these indirect and direct pathways to reach the lysosome
Secretory granules
Endocrine, exocrine, and neuronal cells use a third sorting pathway from the TGN to concentrate and package selected proteins in ____ ____
Proteins
Regulated secretory pathway is used to store and discharge secreted ____ in response to stimulation
Immature; mature
Secreted proteins bud from the TGB as _____ secretory granules (iSG) and _____ during storage (mSG)
Proteolytic; C-peptide
Pro insulin granules bud from the TGN and are cleaved by ____ enzymes to remove the __-peptide, which precipitates and leaves mature insulin
H+ and Zn2+
The combination of a ___-ATPase and a ____ transporter in the membrane of secretory granule vesicles helps aggregate and concentrate secretory proteins in secretory granules
Hydrolases; mannose; M-6-P
Enzymes in the cis-Golgi mark at least 50 different ______ for transport to lysosomes by phosphorylating the 6-hydroxyl of ____ to make ___
Kinds of hydrolases
Glycosidases, proteases, lipases, nucleases, and sulfatases
Lysosomal; receptors (MPRs); trans
The making of M-6-P is the sorting signal that directs _______ enzymes to M-6-P _____ in the ___-golgi for tarting to lysosomes
Clathrin
Sorting motifs in the cytoplasmic tails of MPRs target the receptor and bound lysosomal enzymes to ____-coated vesicles in the TGN for delivery to lysosomes
AP1
Interacts wit the cytoplasmic tail of MPR, Arf1-GTP, and PI(4)P on the TGN membrane to recruit clathrin to assemble a budding vesicle