17.5
Mantelaufbau und GTPasen
Vesikel enthalten unterschiedliche Hüllprotein-Untereinheiten an unterschiedlichen Zellstandorten, wodurch sich die Eigenschaften der Hülle, wie etwa…
Vesikelhüllen bestehen aus Hüllprotein-Untereinheiten und Adapterproteinen. Adapterproteine nutzen ihre PIP-Bindungsdomänen, um mit PIPs zu interagieren und die zytosolische Seite der Plasmamembran zu biegen. Dadurch können die Untereinheiten des Hüllproteins an die Membran binden.
GTP-bindende Proteine wie Sar1, eine kleine GTPase im ER, regulieren die Rekrutierung von Hüllproteinen, um den Ort und den Zeitpunkt der Bildung und Fusion von COPII-Vesikeln zu kontrollieren. Sie wechseln zwischen einem BIP-gebundenen inaktiven Zustand und einem GTP-gebundenen aktiven Zustand.
Guanin-Nukleotid-Austauschfaktoren oder GEFs katalysieren den Austausch von GDP gegen GTP im Protein, während GTPase-aktivierende Proteine oder GAPs die Hydrolyse von GTP katalysieren und somit die Proteine deaktivieren.
Der inaktive, zytoplasmatische Sar1-GDP-Komplex bindet Sar1-GEF, das sich in der ER-Membran befindet. Infolgedessen ersetzt GTP GDP auf Sar1 und legt eine amphiphile Helix frei, die mit der ER-Membran interagiert.
Der ER-gebundene Sar1-GTP-Komplex rekrutiert COPII-Adapterproteine – den Sec23/24-Subkomplex. Dadurch können sich die Hüllproteine zusammensetzen und die Vesikelknospung einleiten.
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Q1: What are the main components of vesicle coats?
Vesicle coats consist of coat protein subunits and adaptor proteins that work together to form the vesicle structure. Adaptor proteins bind to phosphatidylinositol phosphates (PIPs) on the membrane and bend the cytosolic side, allowing coat protein subunits to attach. This coordinated assembly initiates membrane budding and vesicle formation at specific cellular locations.
Q2: How do GTPases regulate coat protein assembly?
Small GTPases like Sar1 control coat assembly by switching between inactive GDP-bound and active GTP-bound states. GEFs catalyze GDP-to-GTP exchange to activate GTPases, while GAPs promote GTP hydrolysis to deactivate them. This molecular switch ensures coat proteins assemble only when and where vesicle formation is needed.
Q3: What is the role of adaptor proteins in vesicular traffic?
Adaptor proteins link coat proteins to the membrane and control vesicular traffic by identifying specific compartments and determining when and where coat assembly occurs. They bind to transmembrane cargo receptors and are specific for particular cargo types, thus playing a crucial role in cargo selectivity and ensuring distinct adaptor proteins regulate budding from different membranes.
Q4: How does Sar1-GTP initiate COPII vesicle formation?
Inactive Sar1-GDP binds Sar1-GEF at the ER membrane, triggering GTP exchange. The resulting Sar1-GTP exposes an amphiphilic helix that inserts into the ER membrane. This activated complex then recruits COPII adaptor proteins, specifically the Sec23/24 subcomplex, which allows coat proteins to assemble and begin membrane budding.
Q5: Why are different coat proteins used in different cell locations?
Different coat protein subunits are incorporated at different cellular locations, which changes coat properties such as shape and geometry of transport vesicles. This variation allows cells to tailor vesicle characteristics to specific transport needs. ARF regulates COPI and clathrin coats at the Golgi, while Sar1 regulates COPII coats at the ER.
Q6: What happens when GEFs and GAPs regulate GTPase activity?
Guanine nucleotide exchange factors (GEFs) catalyze GDP-to-GTP exchange, activating GTPases and promoting coat protein recruitment. GTPase activating proteins (GAPs) catalyze GTP hydrolysis, deactivating GTPases and terminating coat assembly. This cycle ensures precise temporal and spatial control of vesicle formation and subsequent membrane fusion events.
Q7: How do adaptor proteins contribute to cargo selection?
Adaptor proteins bind transmembrane receptors involved in cargo capture, indirectly controlling cargo selectivity. Since distinct adaptor proteins are specific for different cargo receptor types, they ensure appropriate cargo is packaged into vesicles budding from particular membranes. This specificity is essential for maintaining proper protein and lipid distribution throughout the cell.