Evidence for a primary endocytic vesicle involved in synaptic vesicle biogenesis.
The regulated release of neurotransmitters at synapses is mediated by the fusion of neurotransmitter-filled synaptic vesicles with the plasma membrane. Continuous synaptic activity relies on the constant recycling of synaptic vesicle proteins into newly formed synaptic vesicles. At least two different mechanisms are presumed to mediate synaptic vesicle biogenesis at the synapse as follows: direct retrieval of synaptic vesicle proteins and lipids from the plasma membrane, and indirect passage of synaptic vesicle proteins through an endosomal intermediate. We have identified a vesicle population with the characteristics of a primary endocytic vesicle responsible for the recycling of synaptic vesicle proteins through the indirect pathway. We find that synaptic vesicle proteins colocalize in this vesicle with a variety of proteins known to recycle from the plasma membrane through the endocytic pathway, including three different glucose transporters, GLUT1, GLUT3, and GLUT4, and the transferrin receptor. These vesicles differ from "classical" synaptic vesicles in their size and their generic protein content, indicating that they do not discriminate between synaptic vesicle-specific proteins and other recycling proteins. We propose that these vesicles deliver synaptic vesicle proteins that have escaped internalization by the direct pathway to endosomes, where they are sorted from other recycling proteins and packaged into synaptic vesicles.
Provoda
C J
CJ
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Waring
M T
MT
Buckley
K M
KM
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000378:metabolism*; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D016716:PC12 Cells; D051381:Rats; D013572:Synaptic Vesicles / Q000502:physiology*; D016708:Synaptophysin / Q000032:analysis
D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C495679:Slc2a1 protein, rat; C495690:Slc2a3 protein, rat; C495694:Slc2a4 protein, rat; D016708:Synaptophysin