KIF3A/B: a heterodimeric kinesin superfamily protein that works as a microtubule plus end-directed motor for membrane organelle transport.

Abstract

Abstract. We cloned a new member of the murine brain kinesin superfamily, KIF3B, and found that its amino acid sequence is highly homologous but not identical to KIF3A, which we previously cloned and named KIF3 (47% identical). KIF3B is localized in various organ tissues and developing neurons of mice and accumulates with anterogradely moving membranous organelles after ligation of nerve axons. Immunoprecipitation assay of the brain revealed that KIF3B forms a complex with KIF3A and three other high molecular weight (~100 kD)-associated polypeptides, called the kinesin superfamily-associated protein 3 (KAP3). In vitro reconstruction using baculovirus expression systems showed that KIF3A and KIF3B directly bind with each other in the absence of KAP3. The recombinant KIF3A/B complex (~50-nm rod with two globular heads and a single globular tail) demonstrated plus end-directed microtubule sliding activity in vitro. In addition, we showed that KIF3B itself has motor activity in vitro, by making a complex of wild-type KIF3B and a chimeric motor protein (KIF3B head and KIF3A rod tail). Subcellular fractionation of mouse brain homogenates showed a considerable amount of the native KIF3 complex to be associated with membrane fractions other than synaptic vesicles. Immunoprecipitation by anti-KIF3B antibody-conjugated beads and its electron microscopic study also revealed that KIF3 is associated with membranous organelles. Moreover, we found that the composition of KAP3 is different in the brain and testis. Our findings suggest that KIF3B forms a heterodimer with KIF3A and functions as a new microtubule-based anterograde translocator for membranous organelles, and that KAP3 may determine functional diversity of the KIF3 complex in various kinds of cells in vivo.mature neuronal cell has a polarized morphology comprised of dendrites, a long axon, and synapses.

Two Kinesin Light Chain Genes in Mice

“…Thus, an efficient cellular transport mechanism is required, possibly involving several families of molecular motors, each performing a unique function. At least 10 different kinesin-like molecules have already been identified (37,43,45,(47)(48)(49)(50)(51) in mouse brain, and more remain to be discovered. Given the complex organization of the mammalian neuron, it is possible that the two kinesin light chains in mouse perform different functions within the cell, although they may be functionally redundant.…”

Synaptic transmission at retinal ribbon synapses

“…The concept of the ribbon as a molecular motor shuttling vesicles to the active zone was originally proposed by Bunt (1971), and the immunocytochemical localization of KIF3A to the ribbon is compatible with this long-standing hypothesis. However, KIF3A is not exclusively localized to synaptic ribbons: it is also found on some synaptic vesicles (Muresan et al, 1998(Muresan et al, , 1999 as well as on many cargo vesicles in the brain, where it mediates anterograde fast axonal transport (Kondo et al, 1994;Yamazaki et al, 1995;Hirokawa and Takemura, 2004). Thus, a possible function of KIF3A may be to transport active zone structures from the soma to the active zone (e.g., Garner et al, 2000;Kondo et al, 1994;Muresan et al, 1998Muresan et al, , 1999.…”

The Molecular Mechanism of NELL2 Movement and Secretion in Hippocampal Progenitor HiB5 Cells

“…For example, a kinesin motor protein, KIF1A, moves anterogradely along neurites with an average velocity of 1.0 μm/s and retrogradely at 0.72 μm/s in cultured hippocampal neurons (Lee et al, 2003). KIF2 and KIF3 move with a velocity ranging from 0.3-0.5 μm/s (Noda et al, 1995;Yamazaki et al, 1995). Moreover, approximately 70% of the NELL2 vesicles in motion were anterogradely and rapidly transported, similar to most members of the kinesin family (~80%) along the microtubules (Goldstein and Yang, 2000;Lee et al, 2003).…”