Enhancement of neurite-sprouting by suppression of HPC-1/syntaxin 1A activity in cultured vertebrate nerve cells.
HPC-1/syntaxin 1A is a C-terminal anchored neuronal membrane protein, of which all of the N-terminal regions are located on the intracellular side, and it interacts with presynaptic membrane proteins, synaptic vesicle proteins and soluble N-ethylmaleimide-sensitive fusion protein attachment proteins (SNAPs). HPC-1/syntaxin 1A has been proposed to act as a target SNAP receptor (t-SNARE) in the neuron and contributes to the vesicle docking/fusion process during the fast exocytosis at the presynaptic active zone. However, studies using an electron-microscope revealed that HPC-1/syntaxin 1A distributed not only at the presynaptic region but throughout the whole axonal membrane, and the functions of this axonal HPC-1/syntaxin 1A remain completely unknown. To investigate its physiological role, we attempted to inhibit the function of HPC-1/syntaxin 1A in cultured neural cells by following two methods. First, de novo synthesis of HPC-1/syntaxin 1A was inhibited by an application of antisense oligonucleotide in cultured adult rat dorsal root ganglion (DRG) neurons. Second, antibody against HPC-1/syntaxin 1A was applied intra-axonally in the cultured chick retinal ganglion neuron. Both treatments, which were expected to downregulate the function of HPC-1/syntaxin 1A, consistently elicited an enhancement of the axonal sprouting. These results suggest that the axonal HPC-1/syntaxin 1A would physiologically suppress the excess axon-collateral sprouting. Downregulation of HPC-1/syntaxin 1A expression may underlie the control of collateral sprouting and synapse formation during development and memory processes.
Yamaguchi
K
K
Department of Physiology, Kyorin University School of Medicine, Tokyo, Japan.
Nakayama
T
T
Fujiwara
T
T
Akagawa
K
K
D000818:Animals; D002452:Cell Count / Q000187:drug effects*; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology*; D008565:Membrane Proteins / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D050765:Qa-SNARE Proteins; D051381:Rats; D017208:Rats, Wistar; D050827:Syntaxin 1
D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D050765:Qa-SNARE Proteins; C494213:Stx1a protein, rat; D050827:Syntaxin 1