A major mutation of KIF21A associated with congenital fibrosis of the extraocular muscles type 1 (CFEOM1) enhances translocation of Kank1 to the membrane

Kakinuma, Naoto; Kiyama, Ryoiti

doi:10.1016/j.bbrc.2009.06.109

Cited by 39 publications

(27 citation statements)

References 16 publications

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“…1C). These results were in agreement with earlier reports of BIG1-KIF21A (29) and KANK1-KIF21A associations (30), and also with the possibility of KANK1 as a component of some BIG1 complexes. In further experiments, we used siRNA that decreased endogenous KANK1 to 4 ± 3% and KIF21A to 9 ± 5% of control cells (Fig.…”

Section: Resultssupporting

confidence: 83%

“…Co-IP of endogenous KIF21A with BIG1 was not altered after KANK1 depletion, but BIG1 IP after KIF21A depletion yielded significantly less KANK1 than it did from control cells (Fig. 1D), consistent with the notion that co-IP of KANK1 with BIG1 was due, in some part, to its interaction with KIF21A (30). The small amounts of KANK1 in BIG1 IP from cells after ∼90% depletion of KIF21A were still ∼40% of that from control cells (Fig.…”

Section: Resultssupporting

confidence: 76%

“…Kakinuma and Kiyama reported an interaction of KIF21A and KANK1 that influenced membrane localization of KANK1 (30). The human KANK1 gene was first described as a growth suppressor in renal carcinoma cells (31).…”

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confidence: 99%

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Effects of brefeldin A-inhibited guanine nucleotide-exchange (BIG) 1 and KANK1 proteins on cell polarity and directed migration during wound healing

Li¹,

Kuo

Waterman‐Storer

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Brefeldin A-inhibited guanine nucleotide-exchange protein (BIG) 1 activates class I ADP ribosylation factors (ARFs) by accelerating the replacement of bound GDP with GTP to initiate recruitment of coat proteins for membrane vesicle formation. Among proteins that interact with BIG1, kinesin family member 21A (KIF21A), a plusend-directed motor protein, moves cargo away from the microtubule-organizing center (MTOC) on microtubules. Because KANK1, a protein containing N-terminal KN, C-terminal ankyrin-repeat, and intervening coiled-coil domains, has multiple actions in cells and also interacts with KIF21A, we explored a possible interaction between it and BIG1. We obtained evidence for a functional and physical association between these proteins, and found that the effects of BIG1 and KANK1 depletion on cell migration in woundhealing assays were remarkably similar. Treatment of cells with BIG1-or KANK1-specific siRNA interfered significantly with directed cell migration and initial orientation of Golgi/MTOC toward the leading edge, which was not mimicked by KIF21A depletion. Although colocalization of overexpressed KANK1 and endogenous BIG1 in HeLa cells was not clear microscopically, their reciprocal immunoprecipitation (IP) is compatible with the presence of small percentages of each protein in the same complexes. Depletion or overexpression of BIG1 protein appeared not to affect KANK1 distribution. Our data identify actions of both BIG1 and KANK1 in regulating cell polarity during directed migration; these actions are consistent with the presence of both BIG1 and KANK1 in dynamic multimolecular complexes that maintain Golgi/MTOC orientation, differ from those that might contain all three proteins (BIG1, KIF21A, and KANK1), and function in directed transport along microtubules.

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Section: Resultssupporting

confidence: 83%

Section: Resultssupporting

confidence: 76%

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Effects of brefeldin A-inhibited guanine nucleotide-exchange (BIG) 1 and KANK1 proteins on cell polarity and directed migration during wound healing

Li¹,

Kuo

Waterman‐Storer

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Therefore, axonal transport of a molecule requires not only a molecular motor (kinesin or myosin) but also interaction of motor-cargo complex with AIS components, which allows the complex to pass through the AIS. Recently, it has been reported that the third and fourth coiledcoil domains of the KIF21A stalk can interact with the ankyrin-repeat domain (Kakinuma and Kiyama, 2009), implying that the KIF21A (motor)-NCKX2 (cargo) complex is transported to the axon by interacting with ankyrin-G of AIS.…”

Section: Discussionmentioning

confidence: 99%

KIF21A-Mediated Axonal Transport and Selective Endocytosis Underlie the Polarized Targeting of NCKX2

Lee¹,

Lee²,

Lee³

et al. 2012

J. Neurosci.

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We have previously shown that K ϩ -dependent Na ϩ /Ca 2ϩ exchanger (NCKX) is a major calcium clearance mechanism at the large axon terminals of central neurons, whereas their somata display little NCKX activity. We investigated mechanisms underlying the axonal polarization of NCKX2 in rat hippocampal neurons. We identified NCKX2 as the first neuron-specific cargo molecule of kinesin family member 21A (KIF21A). The intracellular loop of NCKX2 specifically interacted with the WD-40 repeats, a putative cargo-binding domain, of KIF21A. Dominant-negative mutant or depletion of KIF21A inhibited the transport of NCKX2-GFP to axon fibers. Knockdown of KIF21A caused calcium dysregulation at axonal boutons but not at somatodendritic regions. Despite the axonal polarization of the NCKX activity, both somatodendritic and axonal regions were immunoreactive to NCKX2. The surface expression of NCKX2 revealed by live-cell immunocytochemistry, however, displayed highly polarized distribution to the axon. Inhibition of endocytosis increased the somatodendritic surface NCKX2 and thus abolished the axonal polarization of surface NCKX2. These results indicate that KIF21A-mediated axonal transport and selective somatodendritic endocytosis underlie the axonal polarized surface expression of NCKX2.

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“…Only 12 missense mutations in KIF21A have been reported (4,5,(8)(9)(10): two of them are located in the motor domain (C28W located in exon2 and M356T located in exon8) and the rest are clustered in the third coiledcoil region (E944Q, M947V, M947R, M947I and M947T in exon20 and R954W, R954Q, R954L, A1008P and I1010T in exon21). Substitution changes may affect the dimer formation of KIF21A (14,15). By contrast, p.Asp1001del was predicted to change the structure of the following heptad repeat units with a subsequent impact on the electrostatic potential, which may be the cause of the CFEOM phenotype in the QT742 family.…”

Section: Discussionmentioning

confidence: 97%

KIF21A novel deletion and recurrent mutation in patients with congenital fibrosis of the extraocular muscles-1

Wang

Li²,

Xiao³

et al. 2011

Int J Mol Med

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A major mutation of KIF21A associated with congenital fibrosis of the extraocular muscles type 1 (CFEOM1) enhances translocation of Kank1 to the membrane

Cited by 39 publications

References 16 publications

Effects of brefeldin A-inhibited guanine nucleotide-exchange (BIG) 1 and KANK1 proteins on cell polarity and directed migration during wound healing

Effects of brefeldin A-inhibited guanine nucleotide-exchange (BIG) 1 and KANK1 proteins on cell polarity and directed migration during wound healing

KIF21A-Mediated Axonal Transport and Selective Endocytosis Underlie the Polarized Targeting of NCKX2

KIF21A novel deletion and recurrent mutation in patients with congenital fibrosis of the extraocular muscles-1

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