* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download The Exocytic/Lysosomal Transport Pathway
Ancestral sequence reconstruction wikipedia , lookup
Biochemistry wikipedia , lookup
Molecular evolution wikipedia , lookup
Silencer (genetics) wikipedia , lookup
Theories of general anaesthetic action wikipedia , lookup
Gene expression wikipedia , lookup
Molecular neuroscience wikipedia , lookup
Cell-penetrating peptide wikipedia , lookup
Cell membrane wikipedia , lookup
Acetylation wikipedia , lookup
Magnesium transporter wikipedia , lookup
Nuclear magnetic resonance spectroscopy of proteins wikipedia , lookup
G protein–coupled receptor wikipedia , lookup
Model lipid bilayer wikipedia , lookup
Interactome wikipedia , lookup
Protein moonlighting wikipedia , lookup
Protein adsorption wikipedia , lookup
List of types of proteins wikipedia , lookup
Two-hybrid screening wikipedia , lookup
Protein–protein interaction wikipedia , lookup
Western blot wikipedia , lookup
Intrinsically disordered proteins wikipedia , lookup
Vesicular Trafficking Movement From the ER Through the Golgi Getting to the Golgi Anterograde and Retrograde Traffic Genetic Analysis of ER-Golgi Transport General Principles • Cargo selection – signals (ie amino acid sequences) • Vesicle formation (budding) from donor compartment • Vesicle/Cargo targeting and fusion to acceptor compartment • Most regulation is mediated by cargo- and target-compartment-specific small GTPases • Anterograde transport – COPII apparatus – protein complex mediating cargo selection and assembly of budding components from ER • Retrograde transport – COPI – protein complex mediating transfer of vesicles back to ER Retrograde Transport Gives Golgi Compartments Dynamic Identity Cargo Selection: Export Targeting Sequences • Y xnDxE – tyrosine-diacidic domain • Found in cytoplasmic tail of TM proteins Cargo Selection: Just Getting the Right Stuff • Exclusion of ER resident proteins – not well understood – fidelity factors (genes) • mutations in some genes cause increased excretion of ER resident proteins – Retrieval • COPI vesicles retrieve ER proteins and return them • KDEL signal on lumenal proteins • KKxx-COOH on TM proteins (dilysine motif) COPII Vesicular Coat Assembly & Budding • COPII coat formation regulated by sar1 GTPase • sar1 activates cargo receptors – TM proteins recognizing export signals • sar1 recruits sec23/24 coatamer proteins • sec23/24 in turn recruit sec31/13 coat proteins • COPII vesicles form and bud • Once apart from ER, coat proteins are triggered to release by hydrolysis of GTP by sar1 Vesicular Delivery • Rab-GTPases • Recruits tether and fusion proteins into vesicles • These form a targeting complex recognized by a docking complex • targeting – v-tethers – p115 – vSNAREs – synaptobrevin • docking – t-tethers – GRASP65 – tSNAREs – syntaxin 1 Tethering and Fusion Mediated by SNAREs (SNAP Receptors) • SNAREs aggregated by Rab-GTPase (vSNAREs) • Vesicle buds • SNAP25-NSF interact with vesicle to dis-aggregate and prime vSNAREs for interaction with tSNAREs COPI Vesicles Recycle ER Resident Proteins • COPI Vesicles – Arf family of small GTPases – Recruit/activate coatomer (6 cytosolic proteins) – Recruit ER targeting SNAREs Retrieval of ER Proteins with KDEL Signal by COPI Vesicles Cycle of Vesicular Transport Cargo Sorting by the Trans-Golgi Network (TGN) • Specific coat proteins direct TGN vesicles to targets Lysosomal/Endosomal Targeting • Mannose-6-phosphate receptor targeting to lysosome/endosome • MPR cytoplasmic tail (C-term) has multiple signals for multiple routing possibilities Lysosomal Targeting of Prohydrolase by M6P and MPRs •Mannose-6-Phosphate Receptors •Cation-independent (CI) •Cation dependent (CD) Cytoplasmic Tails of MPRs Allow Sorting to Lysosomes vs Other Routes Assembly of Clathrin on Lysosomal/Endosomal Destined TGN Vesicles Directed Translocation of Secretory Vesicles • apical targeting in caveolin coated, lipidraft vesicles • basolateral targeting signals – direct protein to this membrane • constitutive basolateral targeting – subsequent sorting of apical proteins • untargeted vesicles – sorting to redistribute surface proteins Proteolytic Processing of Pro-proteins in Secretory Vesicles • Cleavage of proinsulin in secretory vesicles of pancreas cells Secretory Vesicles/Granules • Material in secretory vesicle aggregates due to decreased pH and divalent cations • Membrane recycling to TGN directly or via endosome reduced vesicle size Regulated Secretion • Fusion of the vesicle and plasma membrane is regulated by various means – receptor-ligand interaction and second messenger signaling – depolarization of membrane – etc…