Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2

Stable Identifier
R-HSA-5666169
Type
Reaction [binding]
Species
Homo sapiens
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The recruitment of DIAPH2-2 (DIA-12C, mDia3) to kinetochores by activated CDC42 (CDC42:GTP) and DIAPH2-2 phosphorylation by AURKB positively regulates the attachment of microtubules to kinetochores (Yasuda et al. 2004, Cheng et al. 2011).

The human kinetochore, is a complex proteinaceous structure that assembles on centromeric DNA and mediates the association of mitotic chromosomes with spindle microtubules in prometaphase. The molecular composition of the human kinetochore is reviewed in detail in Cheeseman et al., 2008. This complex structure is composed of numerous protein complexes and networks including: the constitutive centromere-associated network (CCAN) containing several sub-networks such as (CENP-H, I, K), (CENP-50/U, O, P, Q, R), the KMN network (containing KNL1, the Mis12 complex, and the Ndc80 complex), the chromosomal passenger complex, the mitotic checkpoint complex, the nucleoporin 107-160 complex and the RZZ complex.
At prometaphase, following breakdown of the nuclear envelope, the kinetochores of condensed chromosomes begin to interact with spindle microtubules. In humans, 15-20 microtubules are bound to each kinetochore (McEwen et al., 2001), and the attachment of 15 microtubules to the kinetochore is shown in this reaction. Recently, it was found that the core kinetochore-microtubule attachment site is within the KMN network and is likely to be formed by two closely apposed low-affinity microtubule-binding sites, one in the Ndc80 complex and a second in KNL1 (Cheeseman et al., 2006).

Literature References
PubMed ID Title Journal Year
16622420 The CENP-H-I complex is required for the efficient incorporation of newly synthesized CENP-A into centromeres

Okada, M, Cheeseman, IM, Hori, T, Okawa, K, McLeod, IX, Yates, JR 3rd, Desai, A, Fukagawa, T

Nat Cell Biol 2006
17030981 Mapping the assembly pathways that specify formation of the trilaminar kinetochore plates in human cells

Liu, ST, Rattner, JB, Jablonski, SA, Yen, TJ

J Cell Biol 2006
21397845 Aurora B regulates formin mDia3 in achieving metaphase chromosome alignment

Cheng, L, Zhang, J, Ahmad, S, Rozier, L, Yu, H, Deng, H, Mao, Y

Dev. Cell 2011
15085137 Cdc42 and mDia3 regulate microtubule attachment to kinetochores

Yasuda, S, Oceguera-Yanez, F, Kato, T, Okamoto, M, Yonemura, S, Terada, Y, Ishizaki, T, Narumiya, S

Nature 2004
16622419 The human CENP-A centromeric nucleosome-associated complex

Foltz, DR, Jansen, LE, Black, BE, Bailey, AO, Yates, JR 3rd, Cleveland, DW

Nat Cell Biol 2006
18097444 Molecular architecture of the kinetochore-microtubule interface

Cheeseman, IM, Desai, A

Nat Rev Mol Cell Biol 2008
17129783 The conserved KMN network constitutes the core microtubule-binding site of the kinetochore

Cheeseman, IM, Chappie, JS, Wilson-Kubalek, EM, Desai, A

Cell 2006
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