Regional and developmental regulation of syntaphilin expression in the brain: a candidate molecular element of synaptic functional differentiation.
The conserved nature of the basic machinery underlying synaptic function makes it necessary to search for other factors--structural and molecular--that could account for the tremendous diversity found among synapses even within a single neuron. Syntaphilin is a presynaptic membrane protein previously described as a molecular clamp that controls free syntaxin-1A and dynamin-1 availability, and thereby regulates synaptic vesicle exocytosis and endocytosis at the nerve terminal. In this study, we report our finding that syntaphilin expression is developmentally regulated, and show that syntaphilin is expressed most prominently in the mature rat brain, in areas that have been previously characterized to undergo synaptic plastic change. We also find that syntaphilin undergoes divergent subcellular targeting to the mitochondrial outer membrane and the synaptic plasma membrane, giving rise to two neuronal subpopulations of the protein that are modified in their relative enrichment with synaptic maturation and with the formation of cell contacts. Finally, we demonstrate that syntaphilin expression is initiated with induction of neuronal differentiation in PC12 cells. Given its biochemical and functional properties, the spatially and temporally limited nature of syntaphilin expression provides evidence that syntaphilin could be a molecular element of synaptic functional differentiation.
Das
Sunit
S
Synaptic Function Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 36, Room 5A-23, 36 Convent Drive, Bethesda, MD 20892-4154, USA.
Boczan
Judit
J
Gerwin
Claudia
C
Zald
Philip B
PB
Sheng
Zu-Hang
ZH
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins; D016253:Microscopy, Immunoelectron; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000235:genetics / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism / Q000648:ultrastructure; D050827:Syntaxin 1; D013997:Time Factors; D033921:Vesicular Transport Proteins
D000954:Antigens, Surface; D002352:Carrier Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C405513:SNPH protein, human; C494212:STX1A protein, human; C494213:Stx1a protein, rat; D016708:Synaptophysin; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins; D045304:Cytochromes c; D020932:Nerve Growth Factor