Transport route for synaptobrevin via a novel pathway of insertion into the endoplasmic reticulum membrane.
Synaptobrevin/vesicle-associated membrane protein is one of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. It is proposed to provide specificity for the targeting and fusion of vesicles with the plasma membrane. It belongs to a class of membrane proteins which lack a signal sequence and contain a single hydrophobic segment close to their C-terminus, leaving most of the polypeptide chain in the cytoplasm (tail-anchored). We show that in neuroendocrine PC12 cells, synaptobrevin is not directly incorporated into the target organelle, synaptic-like vesicles. Rather, it is first inserted into the endoplasmic reticulum (ER) membrane and is then transported via the Golgi apparatus. Its insertion into the ER membrane in vitro occurs post-translationally, is dependent on ATP and results in a trans-membrane orientation of the hydrophobic tail. Membrane integration requires ER protein(s) different from the translocation components needed for proteins with signal sequences, thus suggesting a novel mechanism of insertion.
Kutay
U
U
Max-Delbrück, Centre for Molecular Medicine, Berlin-Buch.
Ahnert-Hilger
G
G
Hartmann
E
E
Wiedenmann
B
B
Rapoport
T A
TA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D010450:Endopeptidases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016716:PC12 Cells; D011499:Protein Processing, Post-Translational; D011510:Proteolipids / Q000378:metabolism; D050683:R-SNARE Proteins; D051381:Rats
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011510:Proteolipids; D050683:R-SNARE Proteins; C020485:proteoliposomes; D000255:Adenosine Triphosphate; D010450:Endopeptidases