|
Campenot RB, Soin J, Blacker M, Lund K, Eng H, MacInnis BL.
Block of slow axonal transport and axonal growth by brefeldin A in
compartmented cultures of rat sympathetic neurons.
Neuropharmacology. 2003 Jun;44(8):1107-17.
Department of Cell Biology, Faculty of Medicine and Dentistry,
University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
bob.campenot@ualberta.ca
Disruption of the Golgi by brefeldin A (BFA) has been reported
to block fast axonal transport and axonal growth. We used
compartmented cultures of rat sympathetic neurons to investigate
its effects on slow axonal transport. BFA (1 micro g/ml) applied
to cell bodies/proximal axons for 6-20 h disrupted the Golgi,
reversibly blocked axonal growth, and reversibly blocked
anterograde transport of all proteins, including tubulin. The
retrograde transport of nerve growth factor (NGF) was also
blocked. The phosphorylation of Erk1 and Erk2 in response to NGF
was unaffected after 6 h of treatment with BFA, suggesting that
the block of axonal transport was specific and direct.
Consistent with its principal site of action at the Golgi, no
effects were observed when BFA was applied only to the distal
axons. Block of fast anterograde and retrograde axonal transport
is consistent with the role of the Golgi in supplying transport
vesicles. Block of slow axonal transport was surprising, and
further results indicated that transport of tubulin en route
along the axon was arrested by application of BFA to the cell
bodies, suggesting that a continuous supply of anterograde
transport vesicles from the Golgi is required to maintain slow
axonal transport of cytoskeletal proteins.
PMID: 12763103
|
