Structural highlights
Disease
[NUMA1_HUMAN] Acute promyelocytic leukemia.
Function
[NUMA1_HUMAN] Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority if the nuclear volume. Required for maintenance and establishment of the mitotic spindle poles, functionning as a tether linking bulk microtubules of the spindle to centrosomes. May be involved in coordination of the alignment of the mitotic spindle to the cellular polarity axis, which is a prerequisite for asymmetric cell divisions.[1]
Publication Abstract from PubMed
Mitotic progression is orchestrated by the microtubule-based motor dynein, which sustains all mitotic spindle functions. During cell division, cytoplasmic dynein acts with the high-molecular-weight complex dynactin and nuclear mitotic apparatus (NuMA) to organize and position the spindle. Here, we analyze the interaction interface between NuMA and the light intermediate chain (LIC) of eukaryotic dynein. Structural studies show that NuMA contains a hook domain contacting directly LIC1 and LIC2 chains through a conserved hydrophobic patch shared among other Hook adaptors. In addition, we identify a LIC-binding motif within the coiled-coil region of NuMA that is homologous to CC1-boxes. Analysis of mitotic cells revealed that both LIC-binding sites of NuMA are essential for correct spindle placement and cell division. Collectively, our evidence depicts NuMA as the dynein-activating adaptor acting in the mitotic processes of spindle organization and positioning.
Organizational Principles of the NuMA-Dynein Interaction Interface and Implications for Mitotic Spindle Functions.,Renna C, Rizzelli F, Carminati M, Gaddoni C, Pirovano L, Cecatiello V, Pasqualato S, Mapelli M Structure. 2020 May 11. pii: S0969-2126(20)30138-6. doi:, 10.1016/j.str.2020.04.017. PMID:32413290[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Silk AD, Holland AJ, Cleveland DW. Requirements for NuMA in maintenance and establishment of mammalian spindle poles. J Cell Biol. 2009 Mar 9;184(5):677-90. doi: 10.1083/jcb.200810091. Epub 2009 Mar , 2. PMID:19255246 doi:http://dx.doi.org/10.1083/jcb.200810091
- ↑ Renna C, Rizzelli F, Carminati M, Gaddoni C, Pirovano L, Cecatiello V, Pasqualato S, Mapelli M. Organizational Principles of the NuMA-Dynein Interaction Interface and Implications for Mitotic Spindle Functions. Structure. 2020 May 11. pii: S0969-2126(20)30138-6. doi:, 10.1016/j.str.2020.04.017. PMID:32413290 doi:http://dx.doi.org/10.1016/j.str.2020.04.017
