TY - JOUR T1 - Amphiphysin I Antisense Oligonucleotides Inhibit Neurite Outgrowth in Cultured Hippocampal Neurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 93 LP - 103 DO - 10.1523/JNEUROSCI.18-01-00093.1998 VL - 18 IS - 1 AU - Olaf Mundigl AU - Gian-Carlo Ochoa AU - Carol David AU - Vladimir I. Slepnev AU - Alexander Kabanov AU - Pietro De Camilli Y1 - 1998/01/01 UR - http://www.jneurosci.org/content/18/1/93.abstract N2 - Amphiphysin I is an SH3 domain-containing neuronal protein, enriched in axon terminals, which was reported to act as a physiological binding partner for dynamin I in synaptic vesicle endocytosis. Rvs167 and Rvs161, the yeast homologs of amphiphysin I, have been implicated in endocytosis, actin function, and cell polarity. Now we have explored the possibility that amphiphysin I also may have a role in actin dynamics and cell polarity by testing the effect of amphiphysin I suppression on neurite outgrowth. Freshly plated hippocampal neurons were exposed to antisense oligonucleotides via a new delivery system based on a polycationic amphipathic polymer, PS980. Western blot analysis revealed that amphiphysin I levels steadily increased with neuronal differentiation, whereas in antisense-treated cultures amphiphysin I levels were reduced to ∼10% of control levels at 48 hr. Concomitantly, a collapse of growth cones and a severe inhibition of neurite outgrowth and axon formation were observed. A similar effect was observed previously after dynamin I suppression in the same culture system (Torre et al., 1994). We also have found that amphiphysin I and dynamin I colocalize in developing neurons at all developmental stages and that a pool of both proteins is colocalized with actin patches at the leading edge of growth cones. Our findings suggest a conserved role of the amphiphysin protein family in the dynamics of the cortical cell cytoskeleton and provide new evidence for a close functional link between amphiphysin I and dynamin I. ER -