Identification and Classification of 16 New Kinesin Superfamily (KIF) Proteins in Mouse Genome

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Identification and Classification of 16 New Kinesin Superfamily (KIF) Proteins in Mouse Genome 4214 Corrections Proc. Natl. Acad. Sci. USA 96 (1999) Cell Biology. In the article “Identification and classification of Medical Sciences. In the article “CM101-mediated recovery of 16 new kinesin superfamily (KIF) proteins in mouse genome” walking ability in adult mice paralyzed by spinal cord injury” by Terunaga Nakagawa, Yosuke Tanaka, Eiji Matsuoka, Sa- by Artur W. Wamil, Barbara D. Wamil, and Carl G. Heller- toru Kondo, Yasushi Okada, Yasuko Noda, Yoshimitsu Kanai, qvist, which appeared in number 22, October 27, 1998, of Proc. and Nobutaka Hirokawa, which appeared in number 18, Natl. Acad. Sci. USA (95, 13188–13193), the authors request September 2, 1997 of Proc. Natl. Acad. Sci. USA (94, 9654– that the following two corrections be noted. First, the following 9659), the authors request that the following correction be sentence on page 13188, “CM101 is an antipathoangiogenic noted. In Fig. 5, due to a technical error in the genetic mapping polysaccaride (20) derived from group B streptococcus (GBS) program, the cytogenetic map of the mouse kif5B gene was (21) that inhibits angiogenesis and subsequent infiltration of misidentified. The corrected Fig. 5 and legend are reproduced inflammatory cells and thereby formation of granulation below. tissue, which produces scarring (M. Neeman, R. Abramowitch, B.D.W., and C.G.H., unpublished data),” should read “CM101 is an antipathoangiogenic polysaccharide (20) derived from group B streptococcus (GBS) that inhibits angiogenesis (21) and scarring (B.D.W. and C.G.H., unpublished data). Gran- ulation tissue, which produces scarring, contains new capillar- ies and inflammatory cells [Rubin, E. & Farber, J. L., eds. (1994) Pathology (Lippincott, Philadelphia), 2nd Ed., p. 82].” Second, the reference to Dr. Michal Neeman on page 13192, “M. Neeman, personal communication,” should be deleted. FIG. 5. Cytogenetic mapping was performed for some of the known KIFs. (A and B). Examples of the fluorescence in situ hybrid- ization (FISH) mapping (probed for kif5B). (A) The FISH signals on the chromosome (arrows). (B) The same mitotic figure stained with 49,6-diamidino-2-phenylindole (DAPI) to identify chromosome 18. (C) The rest of the results are summarized. Downloaded by guest on September 27, 2021 Proc. Natl. Acad. Sci. USA Vol. 94, pp. 9654–9659, September 1997 Cell Biology Identification and classification of 16 new kinesin superfamily (KIF) proteins in mouse genome TERUNAGA NAKAGAWA,YOSUKE TANAKA,EIJI MATSUOKA,SATORU KONDO,YASUSHI OKADA,YASUKO NODA, YOSHIMITSU KANAI, AND NOBUTAKA HIROKAWA* Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113, Japan Communicated by Setsuro Ebashi, National Institute for Physiological Sciences, Okazaki, Japan, June 30, 1997 (received for review March 25, 1997) ABSTRACT KIF (kinesin superfamily) proteins are mi- kinesin superfamily remains elusive, but it appears that dif- crotubule-dependent molecular motors that play important ferent members are assigned specific cellular functions. In the roles in intracellular transport and cell division. The extent to mouse there are neuron-specific members such as KIF5A (12), which KIFs are involved in various transporting phenomena, nKHC (17), KIF1A (18), and KIFC2 (13) that are apparently as well as their regulation mechanism, are unknown. The not involved in cell division. [Note that Aizawa et al. (12) identification of 16 new KIFs in this report doubles the originally described KIF5. However, further careful studies existing number of KIFs known in the mouse. Conserved revealed that KIF5 consists of three members that are referred nucleotide sequences in the motor domain were amplified by to as KIF5A, -5B, and -5C in this paper. Henceforth, the name PCR using cDNAs of mouse nervous tissue, kidney, and small KIF5A is used for the sequence referred to as KIF5 in Aizawa intestine as templates. The new KIFs were studied with respect et al.] to their expression patterns in different tissues, chromosomal For neurons, our data suggest that certain classes of mem- location, and molecular evolution. Our results suggest that (i) branous organelles are transported separately down the axon there is no apparent tendency among related subclasses of by different motors. For example, KIF1A is associated with KIFs of cosegregation in chromosomal mapping, and (ii) organelles that contain synaptotagmin, synaptophysin, and according to their tissue distribution patterns, KIFs can be Rab3A, but not SV2, syntaxin 1A, or SNAP-25. Motors such divided into two classes–i.e., ubiquitous and specific tissue- as conventional kinesin or KIF3 were not associated with dominant. Further characterization of KIFs may elucidate KIF1A-containing organelle (18). This evidence suggests that unknown fundamental phenomena underlying intracellular different members of the KIF carry different cargos, even transport. Finally, we propose a straightforward nomencla- though the possibility of functional redundancy still remains. ture system for the members of the mouse kinesin superfamily. In neurons, at least, motor molecules other than KIF1A may exist that transport vesicles containing SV2, syntaxin 1A, and The dynamic aspect of intracellular organelle transport and SNAP-25. Thus with our present knowledge of KIF we may be cell division involve proper functioning of microtubule- unable to obtain the overall view of the complex intracellular dependent molecular motors such as kinesin and dynein transport system. These and other considerations strongly superfamily proteins. Since the biochemical identification (1) motivated us to search for the additional members of the KIF. and cDNA cloning (2) of kinesin heavy chain, cDNAs of Initially, based on PCR approach, our group has identified kinesin superfamily genes were genetically identified from seven KIFs—i.e., KIF1A (18), KIF1B (19), KIF2 (20), KIF3A various species (3–6). The deduced amino acid sequences of (21), KIF3B (22), KIF4 (23), and KIF5A (ref. 12; see notes in these members revealed the presence of a motor domain of the previous paragraph) in mouse brain. Three more KIFs high homology, and a more divergent nonmotor domain. The were identified by another PCR strategy (13). In the present latter comprises a large portion of the whole molecule, with study, the search for additional KIFs was intensified further by amino acid sequences that are characteristic for each members. an improved PCR strategy. We identified 16 new members of These findings support the observation by quick-freeze, deep- KIF, virtually doubling the number of known KIFs in the etch electron microscopy techniques that in nerve axons, many mouse. In this report the partial amino acid sequences of these different types of crossbridge structures are observed between new KIFs are presented with the classification based on cellular organelles and microtubules (7, 8). Some of these molecular evolutionary analysis and tissue distribution. We crossbridges were later identified to be kinesin (9). These and also present the chromosomal mapping for some of the known other findings suggest that the machinery for intracellular KIFs. Finally, we propose the use of a simplified nomenclature transport is highly sophisticated, and that a large family of as for the mouse kinesin superfamily. genes encoding the kinesin superfamily is to be expected. Molecular biological approaches were instrumental in iden- tifying members of the kinesin superfamily. Several amino acid MATERIALS AND METHODS motifs in the motor domain, such as IFAYGQT, DLAGSE, Isolation of mRNA. Mice were killed to obtain the following and HIPYR, are highly conserved among species. Fragments material: 0-day-old whole brain, 4-week-old hippocampus, flanked by these sequences can therefore be amplified by PCR 4-week-old olfactory bulb, 4-week-old kidney, and 4-week-old using degenerate oligonucleotide primers. This strategy iden- intestine. Each tissue was dissected from separate mice to tified many kinesin superfamily members in various organisms, such as Drosophila (10, 11), mouse (12, 13), Xenopus (14), fish Data deposition: The sequences reported in this paper have been (15), yeast (3), and rat (16). The reason for the diversity of the deposited in the GenBank database [accession nos. AB001456 (KIF1C), AB001433 (KIF3C), AB001434 (KIF6), AB001435 (KIF7), The publication costs of this article were defrayed in part by page charge AB001436 (KIF8), AB001437 (KIF9), AB001426 (KIF10), AB001427 (KIF11), AB001428 (KIF12), AB001429 (KIF13A), AB001430 payment. This article must therefore be hereby marked ‘‘advertisement’’ in (KIF13B), AB001431 (KIF14), AB001432 (KIF15), AB001425 accordance with 18 U.S.C. §1734 solely to indicate this fact. (KIF16A), AB001423 (KIF16B), AB001424 (KIF17), AB001457 © 1997 by The National Academy of Sciences 0027-8424y97y949654-6$2.00y0 (KIFC3)]. PNAS is available online at http:yywww.pnas.org. *To whom reprint requests should be addressed. 9654 Cell Biology: Nakagawa et al. Proc. Natl. Acad. Sci. USA 94 (1997) 9655 maintain freshness. The rest of the purification procedures are prime kit (Pharmacia). Quick Hyb (Stratagene) was used for performed as described (24). hybridization according to manufacturer’s protocol. The wash Synthesis of First-Strand cDNA. Two hundred units of schedule was 23 SSCy0.1% SDS at 65°C for 10 min (three Super Script II (GIBCOyBRL) reverse transcriptase was used times). For some probes additional wash in 0.13 SSCy0.1% to transcribe 50–500 ng of poly(A)1 RNA per 20 ml
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