Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly

The molecular motor dynein concentrates at the kinetochore region of mitotic chromosomes in animals to accelerate spindle microtubule capture and to control spindle checkpoint signaling. In this study, we describe the molecular mechanism used by the Rod-Zw10-Zwilch complex and the adaptor Spindly to...

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Veröffentlicht in:The Journal of cell biology Jg. 216; H. 4; S. 943
Hauptverfasser: Gama, José B, Pereira, Cláudia, Simões, Patrícia A, Celestino, Ricardo, Reis, Rita M, Barbosa, Daniel J, Pires, Helena R, Carvalho, Cátia, Amorim, João, Carvalho, Ana X, Cheerambathur, Dhanya K, Gassmann, Reto
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 03.04.2017
Schlagworte:
Animals
Caenorhabditis elegans - metabolism
Caenorhabditis elegans - physiology
Carrier Proteins - metabolism
Cell Cycle Proteins - metabolism
Cell Line, Tumor
Chromosomal Proteins, Non-Histone - metabolism
Chromosome Segregation - physiology
Dynactin Complex - metabolism
Dyneins - metabolism
HeLa Cells
Humans
Kinetochores - metabolism
Kinetochores - physiology
Microtubule-Associated Proteins - metabolism
Microtubules - metabolism
Microtubules - physiology
Mitosis - physiology
Spindle Apparatus - metabolism
Spindle Apparatus - physiology
Spindly
kinetochore
mitosis
RZZ complex
BICD2
dynein/dynactin
ISSN:1540-8140, 1540-8140
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Zusammenfassung:The molecular motor dynein concentrates at the kinetochore region of mitotic chromosomes in animals to accelerate spindle microtubule capture and to control spindle checkpoint signaling. In this study, we describe the molecular mechanism used by the Rod-Zw10-Zwilch complex and the adaptor Spindly to recruit dynein to kinetochores in embryos and human cells. We show that Rod's N-terminal β-propeller and the associated Zwilch subunit bind Spindly's C-terminal domain, and we identify a specific Zwilch mutant that abrogates Spindly and dynein recruitment in vivo and Spindly binding to a Rod β-propeller-Zwilch complex in vitro. Spindly's N-terminal coiled-coil uses distinct motifs to bind dynein light intermediate chain and the pointed-end complex of dynactin. Mutations in these motifs inhibit assembly of a dynein-dynactin-Spindly complex, and a null mutant of the dynactin pointed-end subunit p27 prevents kinetochore recruitment of dynein-dynactin without affecting other mitotic functions of the motor. Conservation of Spindly-like motifs in adaptors involved in intracellular transport suggests a common mechanism for linking dynein to cargo.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1540-8140
1540-8140
DOI:10.1083/jcb.201610108