KIF5C, a Novel Neuronal Kinesin Enriched in Motor Neurons

Abstract

Kinesin superfamily proteins (KIFs) are the molecular motors conveying cargos along microtubules. KIF5s, the heavy chains of conventional kinesin (KHC), are originally identified members of KIFs, and neuronal KIF5A and ubiquitous KIF5B have been identified so far. In the present work, we cloned a novel member of KIF5, KIF5C, and generated specific antibodies against three KIF5s to investigate their distribution and functions. KIF5A showed pan-neuronal distribution in the nervous system. KIF5B showed a glial cell distribution pattern in general; however, interestingly, its expression was strongly upregulated in axonelongating neurons, such as olfactory primary neurons and mossy fibers. KIF5C was also a neuronal KIF5 like KIF5A but was highly 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 their formation, such as axonal elongation. Because a large part of KIF5s in adult motor neurons were expected to be KIF5C, we generated mice lacking the kif5C gene to investigate the functions of KIF5C in neurons in living animals. The mutant mice showed smaller brain size but were viable and did not show gross changes in the nervous system. Closer examinations revealed the relative loss of motor neurons to sensory neurons. Because three KIF5s showed high similarity in the amino acid sequence, could rescue the KIF5B mutant cells, and could form heterodimers, we think that there are functional redundancy among the three KIF5s and that KIF5A and KIF5B prevented the KIF5C null mice from the severe phenotype.Key words: kinesin; KIFs; KIF5A; KIF5B; KIF5C; motor neuron; axonal transport; brain; cloning; gene targeting Kinesin superfamily proteins are the molecular motors acting in the microtubule-based motilities of organelles in eukaryotic cells. More than 10 members of the murine kinesin superfamily proteins (KIFs) have been identified in the nervous system (Aizawa et al

Differential trafficking of Kif5c on tyrosinated and detyrosinated microtubules in live cells

“…Whereas Kif5b is ubiquitously expressed, Kif5a and Kif5c are enriched in neurons. The three proteins are highly homologous and functionally redundant (Kanai et al, 2000). We investigated the properties of GFP-Kif5c in neuronal and non-neuronal cells, and confirmed that it moves at a speed similar in vivo to that measured for the same motor in vitro.…”

All kinesin superfamily protein, KIF, genes in mouse and human

“…Previously, we have identified 25 KIFs in mice (11,(18)(19)(20)(21)(22). Most were found by using molecular biological approaches.…”

“…KHCs form a highly related family (KIF5A, KIF5B, and KIF5C). KIF5B is expressed ubiquitously in many tissues (42), whereas KIF5A and KIF5C are specific to nerve tissue (18,22). Kinesin initially was characterized as a motor transporting membranous organelles anterogradely toward the plus end of microtubules and forming a crossbridge between membranous organelle and microtubules in nerve axons (32,39,40,43,44).…”

KLP6: a newly identified kinesin that regulates the morphology and transport of mitochondria in neuronal cells

“…To study the roles of the three kinesins, including KLP6, in transport of mitochondria in neuronal cells, we used the motor domainless GFP fusion proteins, rather than gene silencing, because of both the redundant expression of the KIF5A, -B and -C genes and the alternative splicing of the KIF1B gene in neuronal cells (Aizawa et al, 1992;Tanaka et al, 1998;Kanai et al, 2000;Zhao et al, 2001). After 24 hours incubation with low serum medium containing retinoic acid, almost all axon-like neurites of the control cells contained many clusters of mitochondria (Fig.…”

“…KHC/KIF5 belongs to the kinesin-1 family and is a conventional kinesin that has been conserved evolutionarily. In mice, two brain-specific isoforms (KIF5A and KIF5C) have been identified in addition to a ubiquitous isoform (KIF5B) (Aizawa et al, 1992;Kanai et al, 2000). In mouse disruption of the gene encoding KIF5B is embryonic lethal, and the null mutant cells exhibit mitochondrial clustering at the perinuclear region (Tanaka et al, 1998).…”