KIF2 IS A NEW MICROTUBULE-BASED ANTEROGRADE MOTOR THAT TRANSPORTS MEMBRANOUS ORGANELLES DISTINCT FROM THOSE CARRIED BY KINESIN HEAVY-CHAIN OR KIF3A B/

Kinesin is known as a representative cytoskeletal motor protein that i s engaged in cell division and axonal transport. In addition to the mu tant assay, recent advances using the PCR cloning technique have eluci dated the existence of many kinds of kinesin-related proteins in yeast , Drosophila, and mice. We previously cloned five different members of kinesin superfamily proteins (KIFs) in mouse brain (Aizawa, H., Y. Se kine, R. Takemura, Z. Zhang, M. Nangaku, and N. Hirokawa. 1992. J. Cel l Biol. 119:1287-1296) and demonstrated that one of them, KIF3A, is an anterograde motor (Kondo, S., R. Sato-Yashitake, Y. Noda, H. Aizawa, T. Nakata, Y. Matsuura, and N. Hirokawa. J. Cell Biol. 1994. 125:1095- 1107). We have now characterized another axonal transport motor, KIF2. Different from other KIFs, KIF2 is a central type motor, since its mo tor domain is located in the center of the molecule. Recombinant KIF2 exists as a dimer with a bigger head and plus-end directionally moves microtubules at a velocity of 0.47 +/- 0.11 mu m/s, which is two third s that of kinesin's. Immunocytological examination showed that native KIF2 is abundant in developing axons and that it accumulates in the pr oximal region of the ligated nerves after a 20-h ligation. Soluble KIF 2 exists without a light chain, and KIF2's associated-vesicles, immuno precipitated by anti-KIF2 antibody, are different from those carried b y existing motors such as kinesin and KIF3A. They are also distinct fr om synaptic vesicles, although KIF2 is accumulated in so-called synapt ic vesicle fractions and embryonal growth cone particles. Our results strongly suggest that KIF2 functions as a new anterograde motor, being specialized for a particular group of membranous organelles involved in fast axonal transport.