Evidence for the involvement of KIF4 in the anterograde transport of L1-containing vesicles.
In this study we present evidence about the cellular functions of KIF4. Using subcellular fractionation techniques and immunoisolation, we have now identified a type of vesicle that associates with KIF4, an NH(2)-terminal globular motor domain kinesin-like protein. This vesicle is highly concentrated in growth cones and contains L1, a cell adhesion molecule implicated in axonal elongation. It lacks synaptic vesicle markers, receptors for neurotrophins, and membrane proteins involved in growth cone guidance. In cultured neurons, KIF4 and L1 predominantly localize to the axonal shaft and its growth cone. Suppression of KIF4 with antisense oligonucleotides results in the accumulation of L1 within the cell body and in its complete disappearance from axonal tips. In addition, KIF4 suppression prevents L1-enhanced axonal elongation. Taken collectively, our results suggest an important role for KIF4 during neuronal development, a phenomenon which may be related to the anterograde transport of L1-containing vesicles.
Peretti
D
D
Instituto Investigación Médica Mercedes y Martín Ferreyra (INIMEC-CONICET), 5000 Córdoba, Argentina.
Peris
L
L
Rosso
S
S
Quiroga
S
S
Cáceres
A
A
D000818:Animals; D000918:Antibody Specificity; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005455:Fluorescent Antibody Technique; D020439:Growth Cones / Q000378:metabolism; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism; D016547:Kinesins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008861:Microsomes / Q000737:chemistry / Q000378:metabolism; D008970:Molecular Weight; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D017966:Pyramidal Cells / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051381:Rats; D013572:Synaptic Vesicles / Q000737:chemistry / Q000378:metabolism; D014617:Vacuoles / Q000737:chemistry* / Q000378:metabolism*
D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D016376:Oligonucleotides, Antisense; C089655:Kif4 protein, mouse; D016547:Kinesins