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* Instituto Investigación Médica Mercedes y Martín Ferreyra, 5000 Córdoba, Argentina; In the present study, we present evidence
about the cellular functions of KIF2, a kinesin-like superfamily member having a unique structure in that its
motor domain is localized at the center of the molecule
(Noda Y., Y. Sato-Yoshitake, S. Kondo, M. Nangaku,
and N. Hirokawa. 1995. J. Cell Biol. 129:157-167.). Using subcellular fractionation techniques, isopicnic sucrose density centrifugation of microsomal fractions
from developing rat cerebral cortex, and immunoisolation with KIF2 antibodies, we have now identified a
type of nonsynaptic vesicle that associates with KIF2.
This type of organelle lacks synaptic vesicle markers (synapsin, synaptophysin), amyloid precursor protein,
GAP-43, or N-cadherin. On the other hand, it contains
Departamento Química Biológica,
Facultad Ciencias Químicas (CIQUIBIC) Universidad Nacional de Córdoba/CONICET, 5000 Córdoba, Argentina; and § Department of Neurology (Neuroscience), Harvard Medical School and Center for Neurological Diseases, Department of
Medicine (Division of Neurology), Brigham and Women's Hospital, Boston, Massachusetts 02115
gc, which is a novel variant of the subunit of the IGF-1
receptor, which is highly enriched in growth cone membranes. Both gc and KIF2 are upregulated by NGF in
PC12 cells and highly concentrated in growth cones of
developing neurons. We have also analyzed the consequences of KIF2 suppression by antisense oligonucleotide treatment on nerve cell morphogenesis and the
distribution of synaptic and nonsynaptic vesicle markers. KIF2 suppression results in a dramatic accumulation of gc within the cell body and in its complete disappearance from growth cones; no alterations in the
distribution of synapsin, synaptophysin, GAP-43, or
amyloid percursor protein are detected in KIF2-suppressed neurons. Instead, all of them remained highly enriched at nerve terminals. KIF2 suppression also produces a dramatic inhibition of neurite outgrowth; this
phenomenon occurs after gc has disappeared from
growth cones. Taken collectively, our results suggest an
important role for KIF2 in neurite extension, a phenomenon that may be related with the anterograde
transport of a type of nonsynaptic vesicle that contains
as one of its components a growth cone membrane receptor for IGF-1, a growth factor implicated in nerve
cell development.
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