Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 regulate mitotic and male meiotic spindle bipolarity

He, Shuwen; Gillies, John P.; Zang, Juliana L; Córdoba-Beldad, Carmen M; Yamamoto, Io; Fujiwara, Yasuhiro; Grantham, Julie; DeSantis, Morgan E.; Shibuya, Hiroki

doi:10.1038/s41467-023-37370-7

Cited by 4 publications

(2 citation statements)

References 63 publications

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“…There are two vertebrate homologs of Roadblock: Roadblock-1 and Roadblock-2, sharing 75% sequence identity. Single-molecule studies show that DDB complexes display similar motility in vitro with either homolog [153]. Nevertheless, Roadblock-1 knockout is embryonically lethal, underscoring the non-redundant cellular functions of the homologs [152].…”

Section: Roadblockmentioning

confidence: 99%

“…Nevertheless, Roadblock-1 knockout is embryonically lethal, underscoring the non-redundant cellular functions of the homologs [152]. Recent research has shed light on their distinct roles: while Roadblock-1 is ubiquitously expressed in mouse tissues and plays a crucial role in ensuring the integrity of the mitotic spindle pole, Roadblock-2 is exclusively involved in meiosis [153]. In meiotic cells, Roadblock-2 targets NuMA to the spindle pole, and its absence leads to spindle pole defects, including multipolarity and misalignment [153].…”

Section: Roadblockmentioning

confidence: 99%

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Structure and Function of Dynein’s Non-Catalytic Subunits

Rao,

Gennerich

2024

Cells

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Dynein, an ancient microtubule-based motor protein, performs diverse cellular functions in nearly all eukaryotic cells, with the exception of land plants. It has evolved into three subfamilies—cytoplasmic dynein-1, cytoplasmic dynein-2, and axonemal dyneins—each differentiated by their cellular functions. These megadalton complexes consist of multiple subunits, with the heavy chain being the largest subunit that generates motion and force along microtubules by converting the chemical energy of ATP hydrolysis into mechanical work. Beyond this catalytic core, the functionality of dynein is significantly enhanced by numerous non-catalytic subunits. These subunits are integral to the complex, contributing to its stability, regulating its enzymatic activities, targeting it to specific cellular locations, and mediating its interactions with other cofactors. The diversity of non-catalytic subunits expands dynein’s cellular roles, enabling it to perform critical tasks despite the conservation of its heavy chains. In this review, we discuss recent findings and insights regarding these non-catalytic subunits.

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Section: Roadblockmentioning

confidence: 99%

Section: Roadblockmentioning

confidence: 99%

Structure and Function of Dynein’s Non-Catalytic Subunits

Rao,

Gennerich

2024

Cells

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Multimodal spatiotemporal transcriptomic resolution of embryonic palate osteogenesis

Piña,

Raju,

Roth

et al. 2023

Nat Commun

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The terminal differentiation of osteoblasts and subsequent formation of bone marks an important phase in palate development that leads to the separation of the oral and nasal cavities. While the morphogenetic events preceding palatal osteogenesis are well explored, major gaps remain in our understanding of the molecular mechanisms driving the formation of this bony union of the fusing palate. Through bulk, single-nucleus, and spatially resolved RNA-sequencing analyses of the developing secondary palate, we identify a shift in transcriptional programming between embryonic days 14.5 and 15.5 pinpointing the onset of osteogenesis. We define spatially restricted expression patterns of key osteogenic marker genes that are differentially expressed between these developmental timepoints. Finally, we identify genes in the palate highly expressed by palate nasal epithelial cells, also enriched within palatal osteogenic mesenchymal cells. This investigation provides a relevant framework to advance palate-specific diagnostic and therapeutic biomarker discovery.

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Spermatocytes have the capacity to segregate chromosomes despite centriole duplication failure

Skinner,

Simington,

López-Jiménez

et al. 2024

EMBO Rep

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Centrosomes are the canonical microtubule organizing centers (MTOCs) of most mammalian cells, including spermatocytes. Centrosomes comprise a centriole pair within a structurally ordered and dynamic pericentriolar matrix (PCM). Unlike in mitosis, where centrioles duplicate once per cycle, centrioles undergo two rounds of duplication during spermatogenesis. The first duplication is during early meiotic prophase I, and the second is during interkinesis. Using mouse mutants and chemical inhibition, we have blocked centriole duplication during spermatogenesis and determined that non-centrosomal MTOCs (ncMTOCs) can mediate chromosome segregation. This mechanism is different from the acentriolar MTOCs that form bipolar spindles in oocytes, which require PCM components, including gamma-tubulin and CEP192. From an in-depth analysis, we identified six microtubule-associated proteins, TPX2, KIF11, NuMA, and CAMSAP1-3, that localized to the non-centrosomal MTOC. These factors contribute to a mechanism that ensures bipolar MTOC formation and chromosome segregation during spermatogenesis when centriole duplication fails. However, despite the successful completion of meiosis and round spermatid formation, centriole inheritance and PLK4 function are required for normal spermiogenesis and flagella assembly, which are critical to ensure fertility.

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Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 regulate mitotic and male meiotic spindle bipolarity

Cited by 4 publications

References 63 publications

Structure and Function of Dynein’s Non-Catalytic Subunits

Structure and Function of Dynein’s Non-Catalytic Subunits

Multimodal spatiotemporal transcriptomic resolution of embryonic palate osteogenesis

Spermatocytes have the capacity to segregate chromosomes despite centriole duplication failure

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