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Endocytosis
- what is it?
explain phagocytosis
- i. Endocytosis: process by which the cell internalizes cell-surface receptors and bound extracellular ligands
- ii. Phagocytosis: uptake of particulate matter
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Endocytosis can be divided into what?
- bulk-phase
- 1. receptor mediated
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Explain bulk phase
- 1. bulk-phase: (aka: pinocytosis) nonspecific uptake of EC fluids
- a. any molecules within fluid go into cell
- b. bulk-phase removes portions of the plasma membrane and may function primarily in the recycling of membrane between the cell-surface and interior compartments
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receptor mediated endocytosis
a. brings about the uptake of specific extracellular macromolecules (ligands) following their binding to receptors on the external surface of the plasma membrane
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Receptor-mediated endocytosis and the role of coated pits
i. provides a means for __uptake of macromolecules that may be present at relatively low concentrations in the EC fluid
ii. receptors can take up dif. types of __(hormones, GFs, etc)
iii. substances that enter a cell by means of clathrin-mediated RME become bound to receptors that collect in specialized domains of the plasma membrane, called coated pits
- selective and efficient
- ligands
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1. receptors are concentrated in __ at 10-2__0 times their level in the rest of the plasma membrane
a. __ __ into the cytoplasm and then pinch free of the plasma membrane to form __
ii. from cytoplasmic side, the bristly coat appears as polygons
1. geometric construction of the coat is derived from the structure of its clathrin building blocks
- coated pits
- coated pits
- coated pits invaginate
- coated vesicles
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i. Clathrin
1. Each clathrin molecule consists of __ and __, joined together at the center to form a __ assembly called a __.
a. __in such a way that each __of a polygon contains a center of one of the component __
i. overlap extensively
- three heavy chains and three light chains
- three-legged
- triskelion
- overlap
- vertex
- triskelions
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i. The coated vesicles that form during __also contain a layer of __situated between the __ and the surface of the __ facing the __
1. the best adaptor operating in connection with __ is __
- Endocytosis
- adaptors
- clathrin lattice
- vesicle
- cytosol
- clathrin-mediated Endocytosis
- AP2
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AP2
contain multiple subunits having different functions
- alpha subunit?
i. μ subunit of AP2 adaptors engages the cytoplasmic tails of specific plasma membrane receptors, leading to the concentration of these selected receptors and their bound cargo into the emerging coated vesicles
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AP2
contain multiple subunits having different functions
- beta subunit?
ii. β-adaptin subunit of AP2 adaptors binds and recruits the clathrin molecules of the overlying lattice
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i. coated vesicles may have upwards of __ that form a __ of interacting molecules
1. these proteins have roles in __, __, __, interaction with __components, __, and __
- two dozen different accessory proteins
- dynamic network
- cargo recruitment
- coat assembly
- membrane bending and invagination
- cytoskeletal
- vesicle release
- membrane uncoating
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One is dynamin. Explain it.
i. large GTP-binding protein that is required for the release of a clathrin-coated vesicle from the membrane on which it forms
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i. dynamin self-assembles into a __ around the __of an __, just before it pinches off from the membrane
ii. __of the bound __by the __ molecules induces a twisting motion in the __ that severs the __ from the plasma membrane
1. according to this mechanism, dynamin acts as an enzyme capable of utilizing the chemical energy of __to general mechanical forces
- helical collar
- neck
- invaginated coated pit
- hydrolysis
- GPT
- polymerized dynamin
- dynamin helix
- coated vesicle
- GTP
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1. dissociation of the __from the vesicle requires the help of an additional protein __, which is recruited to the clathrin coat by a cofactor, __
- clathrin coat
- ATPase Hsc70
- auxilin
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i. __also play an important role in formation of coated vesicles
1. __groups can be added to different positions of the sugar ring of the phospholipid __, converting them into __
- phospholipids
- phosphate
- PI
- phosphoinositides
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a. the phosphorylated rings of these __reside at the surface of the membrane where they can be recognized and bound by particular proteins = “__”
- phosphoinositides
- surface identity
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i. The inner leaflet of the plasma membrane tends to contain elevated levels of __, which plays an important role in __
- PI(4,5)P2
- recruiting proteins involved in clathrin-mediated Endocytosis, such as dynamin and AP2
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1. not only can a __aid in recruiting specific proteins, it can also induce __ in a bound protein that facilitate a molecular process
Explain an example.
- phosphoinositide
- conformational changes
a. the clatrhin adaptor AP2, for ex., normally exists in the cytosol in a locked conformation until binding of the AP2 complex to PIP2 causes a conformational change in AP2 that opens a cargo binding site within the adaptor, allowing it to interact with the cytoplasmic tails of specific membrane receptors
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i. a __species like __can have a dynamic regulatory role because it can be __that are localized at particular places and times within the cell
1. in Endocytosis, PIP2 disappears from a site of Endocytosis about the time the coated vesicle is pinched away from the plasma membrane
- lipid
- PIP2
- rapidly formed and destroyed by enzymes
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