Bio202 Lecture 7: Vesicular Transport Part 2 PDF

Lecture 7: Vesicular Transport Part 2 https://doi.org/10.1083/jcb.88.3.564  Today’s agenda - ER to Golgi transport - Exocytosis Membrane enclosed organelles import proteins by one of three mechanisms 1) moved fully-folded through a pore...

Lecture 7: Vesicular Transport Part 2 https://doi.org/10.1083/jcb.88.3.564  Today’s agenda - ER to Golgi transport - Exocytosis Membrane enclosed organelles import proteins by one of three mechanisms 1) moved fully-folded through a pore 2) moved by protein translocators generally as an unfolded polypeptide chain 3) delivered by transport vesicles Figure 15-4 Membrane enclosed organelles import proteins by one of three mechanisms Mechanisms 2 and 3 are required for proteins that are trafficked to the Golgi and beyond! 2) moved by protein translocators generally as an unfolded polypeptide chain 3) delivered by transport vesicles Figure 15-4  The ER is the gateway to the endomembrane system ARROWS secretory pathway endocytic pathway retrieval pathway Figure 15-19 Let’s focus again on ER to Golgi transport Different coats are used for different steps in vesicle transport ARROWS secretory pathway endocytic pathway retrieval pathway COPII vesicles are used for ER to Golgi vesicle traffic  ER to Golgi transport EXIT SIGNALS - commonly an amino acid sequence on the protein - both soluble and membrane-bound cargo proteins have exit signals - membrane-bound proteins with exit signals are either… 1) destined to reside in the membrane of another organelle in the endomembrane system or 2) act as cargo receptors for soluble proteins and are recycled back to the ER exit signal on a membrane-bound cargo protein  ER to Golgi transport The coat serves two main functions: 1) the inner coat serves to concentrate cargo 2) the outer coat, with its curved structure, deforms the membrane and shapes the vesicle  ER to Golgi transport The coat serves two main functions: 1) the inner coat serves to concentrate cargo 2) the outer coat, with its curved structure, deforms the membrane and shapes the vesicle Exit from the ER is controlled to ensure protein quality control Accumulation of misfolded proteins in the ER triggers an unfolded protein response (UPR) Peter Walter Figure 15-25 ER to Golgi transport vesicle uncoats and fuses with the Golgi  Once fused with the target membrane, the cargo receptor releases soluble cargo How? Figure 15-22  Basic model for regulation of binding interactions between cargo receptors and their cargo Golgi Decreasing PH COPI-mediated Golgi to ER vesicle transport recycles cargo receptors modified from Dancourt and Barlowe 2010 Annual Review of Biochemistry  pH difference between organelles pH of individual cellular compartments Casey et al. (2010) Nat Rev Mol Cell Bio  How does cargo get selected for transport? The coat serves two main functions: 1) the inner coat serves to concentrate cargo 2) the outer coat, with its curved structure, deforms the membrane and shapes the vesicle occasionally resident ER proteins get trapped in the vesicle Escaped resident ER proteins can be returned to the ER - Resident ER proteins have an ER retrieval signal - KDEL = ER retrieval signal - The ER retrieval signal is recognized by the KDEL receptor in the Golgi - The KDEL receptor with its bound resident ER protein gets incorporated into COPI coated vesicles - These vesicles bud off the Golgi and fuse with the ER  Different coats are used for different steps in vesicle transport Golgi to ER retrieval pathway ARROWS secretory pathway endocytic pathway retrieval pathway  The ER is the gateway to the endomembrane system ARROWS secretory pathway endocytic pathway retrieval pathway Figure 15-19 Now let’s focus on the Golgi  The Golgi apparatus a series of cisternae, flattened membrane-enclosed compartments cis face A pita bread model of the Golgi trans face Figure 15-26 modified  Modification and sorting of proteins occur in the Golgi apparatus traveling through the Golgi Ready to go to that party elsewhere in the Note - You do not need to memorize the modifications. Just know that proteins endomembrane system! are modified in the Golgi and modification is important for their functions.  Two models of protein transport through the Golgi apparatus vesicle transport model cisternal maturation model Golgi cisternae are long Golgi cisternae are lived structures that retain dynamic structures that their characteristic set of mature from early to late Golgi-resident proteins by acquiring and then firmly in place, and cargo losing specific Golgi- proteins are transported resident proteins from one cisterna to the next by transport vesicles  Two models of protein transport through the Golgi apparatus vesicle transport model cisternal maturation model Trans Cis Courtesy of Ben Glick (UofC)  Two models of protein transport through the Golgi apparatus vesicle transport model cisternal maturation model Golgi cisternae are long Golgi cisternae are lived structures that retain dynamic structures that their characteristic set of mature from early to late Golgi-resident proteins by acquiring and then firmly in place, and cargo losing specific Golgi- proteins are transported resident proteins from one cisterna to the next by transport vesicles Most likely the correct model!  Nest step: Golgi to plasma membrane vesicle transport ARROWS secretory pathway endocytic pathway retrieval pathway Figure 15-19  Exocytosis - excretion of material from the cell by vesicle fusion with the plasma membrane - can occur constitutively or be regulated - supplies newly made lipids and proteins to the plasma membrane - secrets proteins into the extracellular space Figure 15-18  Constitutive versus regulated exocytosis Constitutive pathway: - operates continuously and required in all cells - supplies newly made lipids and proteins to the plasma membrane - secrets proteins into the extracellular space Regulated pathway: - mainly found in cells specialized for secreting products rapidly on demand (hormones, digestive enzymes, neurotransmitters) - secretion usually occurs in response to an extracellular signal  Constitutive versus regulated exocytosis Figure 15-30  The release of neurotransmitters by a neuron - In the nerve terminal of an unstimulated nerve, the vesicles are in the cytosol waiting to receive a signal to dock and fuse with the plasma membrane - In the nerve terminal of a stimulated neuron (shown on the right), a signal is received that stimulates the fusion of the synaptic vesicles with the plasma membrane causing the release of neurotransmitters into the synaptic cleft Figure 15-31  Vesicular transport Next class – endocytosis and autophagy! ARROWS secretory pathway endocytic pathway retrieval pathway Figure 15-19