Organizational Principles of the NuMA-Dynein Interaction Interface and Implications for Mitotic Spindle Functions

Renna, Cristina; Rizzelli, Francesca; Carminati, Manuel; Gaddoni, Chiara; Pirovano, Laura; Cecatiello, Valentina; Pasqualato, Sebastiano; Mapelli, Marina

doi:10.1016/j.str.2020.04.017

Cited by 17 publications

(19 citation statements)

References 51 publications

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“…Furthermore, NuMA and its Drosophila homology Mud link the dynein complex to the cortex via the interaction with membrane localized Gαi, for pulling mitotic spindle poles in dividing cells 65 . Recently, it has been shown that NuMA has a Hook domain and a CC1-Box-like Motif, both of which interact with the effector-binding domain of DLIC 66 . Therefore, Baz/Par-3, SKTL, 14-3-3 ε and ζ, and NuMA/Mud are all potential linkers of Dlic to the cell cortex.…”

Section: Dynein Anchorage At the Cell Cortexmentioning

confidence: 99%

A novel mechanism of bulk cytoplasmic transport by cortical dynein in Drosophila ovary

Lü¹,

Lakonishok²,

Serpinskaya³

et al. 2022

eLife

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Cytoplasmic dynein, a major minus-end directed microtubule motor, plays essential roles in eukaryotic cells. Drosophila oocyte growth is mainly dependent on the contribution of cytoplasmic contents from the interconnected sister cells, nurse cells. We have previously shown that cytoplasmic dynein is required for Drosophila oocyte growth and assumed that it simply transports cargoes along microtubule tracks from nurse cells to the oocyte. Here we report that instead of transporting individual cargoes along stationary microtubules into the oocyte, cortical dynein actively moves microtubules within nurse cells and from nurse cells to the oocyte via the cytoplasmic bridges, the ring canals. This robust microtubule movement is sufficient to drag even inert cytoplasmic particles through the ring canals to the oocyte. Furthermore, replacing dynein with a minus-end directed plant kinesin linked to the actin cortex is sufficient for transporting organelles and cytoplasm to the oocyte and driving its growth. These experiments show that cortical dynein performs bulk cytoplasmic transport by gliding microtubules along the cell cortex and through the ring canals to the oocyte. We propose that the dynein-driven microtubule flow could serve as a novel mode of fast cytoplasmic transport.

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Section: Dynein Anchorage At the Cell Cortexmentioning

confidence: 99%

A novel mechanism of bulk cytoplasmic transport by cortical dynein in Drosophila ovary

Lü¹,

Lakonishok²,

Serpinskaya³

et al. 2022

eLife

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“…Adaptors containing a CC1 box include BICD2 (Chowdhury et al, 2015;Urnavicius et al, 2015), BICDR1 (also known as BICDL1; Grotjahn et al, 2018;Urnavicius et al, 2018) and spindly (Gama et al, 2017;McKenney et al, 2014). Hook-domain adaptors include Hook1, Hook2 and Hook3 (Dwivedi et al, 2019;Olenick et al, 2016;Schroeder and Vale, 2016), as well as NuMA (Renna et al, 2020), although NuMA also contains an additional CC1-like box that engages with dynein LIC. Finally, EF-hand-containing adaptors include FIP3 (McKenney et al, 2014), ninein and ninein-like (Redwine et al, 2017), Rab45 (also known as RASEF) and CRACR2A (Wang et al, 2019).…”

Section: Lic-adaptor Interactions Increase the Cargo Selectivity And Processivity Of Dyneinmentioning

confidence: 99%

Dynein light intermediate chains as pivotal determinants of dynein multifunctionality

Kumari

Kumar

Wasnik

et al. 2021

Journal of Cell Science

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In animal cells, a single cytoplasmic dynein motor mediates microtubule minus-end-directed transport, counterbalancing dozens of plus-end-directed kinesins. The remarkable ability of dynein to interact with a diverse cargo spectrum stems from its tightly regulated recruitment of cargo-specific adaptor proteins, which engage the dynactin complex to make a tripartite processive motor. Adaptor binding is governed by the homologous dynein light intermediate chain subunits LIC1 (DYNC1LI1) and LIC2 (DYNC1LI2), which exist in mutually exclusive dynein complexes that can perform both unique and overlapping functions. The intrinsically disordered and variable C-terminal domains of the LICs are indispensable for engaging a variety of structurally divergent adaptors. Here, we hypothesize that numerous spatiotemporally regulated permutations of posttranslational modifications of the LICs, as well as of the adaptors and cargoes, exponentially expand the spectrum of dynein–adaptor–cargo complexes. We thematically illustrate the possibilities that could generate a vast set of biochemical variations required to support the wide range of dynein functions.

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“…The N-terminal region is required to interact with cytoplasmic dynein and dynactin complexes during mitosis (Kotak et al, 2012). A recent structural study revealed that NuMA 1−153 contains a Hook domain that directly interacts with dynein light intermediate chain (LIC) 1 and 2 (Renna et al, 2020;Figure 2B; all domains are listed in Table 1). The authors also identified a CC1-box like motif, NuMA 360−385 , adjacent to the Hook domain which forms part of the binding interface between NuMA and LIC (Renna et al, 2020;Figure 2B).…”

Section: Dynein-binding Domains In the N-terminal Region Of Numamentioning

confidence: 99%

“…A recent structural study revealed that NuMA 1−153 contains a Hook domain that directly interacts with dynein light intermediate chain (LIC) 1 and 2 (Renna et al, 2020;Figure 2B; all domains are listed in Table 1). The authors also identified a CC1-box like motif, NuMA 360−385 , adjacent to the Hook domain which forms part of the binding interface between NuMA and LIC (Renna et al, 2020;Figure 2B). In addition, NuMA 417−422 contains a Spindly-like motif which is well conserved in vertebrates (Okumura et al, 2018;Tsuchiya et al, 2021), and may interact with the dynactin point-end complex (Gama et al, 2017;Lee et al, 2020).…”

Section: Dynein-binding Domains In the N-terminal Region Of Numamentioning

confidence: 99%

“…In vitro studies suggest that either the N-terminal (199-432 or 1-400 a.a) or C-terminal part (670-1700 a.a.) of the central coiledcoil is sufficient to form a homo-dimer (Harborth et al, 1995;Forth et al, 2014). Dimerization is most likely critical for most NuMA functions, including dynein binding via its N-terminal Hook domain (Renna et al, 2020) and microtubule cross-linking activities via the C-terminal domain (Forth et al, 2014).…”

Section: The Central Long Coiled-coil Domain Of Numamentioning

confidence: 99%

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The Nuclear Mitotic Apparatus (NuMA) Protein: A Key Player for Nuclear Formation, Spindle Assembly, and Spindle Positioning

Kiyomitsu

Boerner

2021

Front. Cell Dev. Biol.

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The nuclear mitotic apparatus (NuMA) protein is well conserved in vertebrates, and dynamically changes its subcellular localization from the interphase nucleus to the mitotic/meiotic spindle poles and the mitotic cell cortex. At these locations, NuMA acts as a key structural hub in nuclear formation, spindle assembly, and mitotic spindle positioning, respectively. To achieve its variable functions, NuMA interacts with multiple factors, including DNA, microtubules, the plasma membrane, importins, and cytoplasmic dynein. The binding of NuMA to dynein via its N-terminal domain drives spindle pole focusing and spindle positioning, while multiple interactions through its C-terminal region define its subcellular localizations and functions. In addition, NuMA can self-assemble into high-ordered structures which likely contribute to spindle positioning and nuclear formation. In this review, we summarize recent advances in NuMA’s domains, functions and regulations, with a focus on human NuMA, to understand how and why vertebrate NuMA participates in these functions in comparison with invertebrate NuMA-related proteins.

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Organizational Principles of the NuMA-Dynein Interaction Interface and Implications for Mitotic Spindle Functions

Cited by 17 publications

References 51 publications

A novel mechanism of bulk cytoplasmic transport by cortical dynein in Drosophila ovary

A novel mechanism of bulk cytoplasmic transport by cortical dynein in Drosophila ovary

Dynein light intermediate chains as pivotal determinants of dynein multifunctionality

The Nuclear Mitotic Apparatus (NuMA) Protein: A Key Player for Nuclear Formation, Spindle Assembly, and Spindle Positioning

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