KIF5C, a novel neuronal kinesin enriched in motor neurons

Kinesin superfamily proteins (KIFs) are the molecular motors conveying carg os along microtubules. KIF5s, the heavy chains of conventional kinesin (KHC ), are originally identified members of KIFs, and neuronal KIF5A and ubiqui tous KIF5B have been identified so far. In the present work, we cloned a no vel member of KIF5, KIF5C, and generated specific antibodies against three KIF5s to investigate their distribution and functions. KIF5A showed pan-neu ronal distribution in the nervous system. KIF5B showed a glial cell distrib ution pattern in general; however, interestingly, its expression was strong ly upregulated in axon-elongating neurons, such as olfactory primary neuron s and mossy fibers. KIF5C was also a neuronal KIF5 like KIF5A but was highl y expressed in lower motor neurons in 2-week-old or older mice, suggesting its important roles in the maintenance of motor neurons rather than in thei r formation, such as axonal elongation. Because a large part of KIF5s in ad ult motor neurons were expected to be KIF5C, we generated mice lacking the kif5C gene to investigate the functions of KIF5C in neurons in living anima ls. The mutant mice showed smaller brain size but were viable and did not s how gross changes in the nervous system. Closer examinations revealed the r elative loss of motor neurons to sensory neurons. Because three KIF5s showe d high similarity in the amino acid sequence, could rescue the KIF5B mutant cells, and could form heterodimers, we think that there are functional red undancy among the three KIF5s and that KIF5A and KIF5B prevented the KIF5C null mice from the severe phenotype.