Transient requirement for vimentin in neuritogenesis: intracellular delivery of anti-vimentin antibodies and antisense oligonucleotides inhibit neurite initiation but not elongation of existing neurites in neuroblastoma.
Vimentin is initially expressed by nearly all neuronal precursors in vivo, and is gradually replaced by neurofilaments shortly after the immature neurons become postmitotic (Cochard and Paulin, 1984, J Neurosci 4:2080; Tapscott et al., 1981, Dev Biol 86:40). A transient increase in neuritic vimentin filaments occurs within the first day of dbcAMP-mediated neurite induction in NB2a/d1 neuroblastoma, after which vimentin levels rapidly decline and neurofilaments increase (Shea, 1990, Brain Res 521:343). In the present study, we tested the possibility that vimentin filaments may function in neurite elaboration by inducing neuritogenesis under conditions where vimentin expression and assembly was inhibited. Intracellular delivery of anti-vimentin antiserum into transiently permeabilized NB2a/d1 cells prevented the initial elaboration of neurites, but did not retract existing neurites. By contrast, intracellular delivery of antiserum directed against the low molecular weight neurofilament subunit or normal rabbit antiserum did not affect neurite outgrowth. Treatment with vimentin antisense oligonucleotides reversibly depleted vimentin synthesis and steady-state levels, and prevented neurite initiation, but did not induce retraction of existing neurites. These findings point toward an hitherto undetected role for vimentin in the initiation of neurite outgrowth.
Shea
T B
TB
Laboratory for Cellular and Developmental Neurobiology, McLean Hospital, Belmont, Massachusetts 02178.
Beermann
M L
ML
Fischer
I
I
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D001483:Base Sequence; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009447:Neuroblastoma; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D014746:Vimentin