VezA/Vezatin Facilitates Proper Assembly of the Dynactin Complex in vivo DOI
Jun Zhang, Rongde Qiu,

Sean Xie

и другие.

Опубликована: Янв. 1, 2024

Cytoplasmic dynein-mediated intracellular transport needs the multi-component dynactin complex for cargo binding and motor activation. However, cellular factors involved in assembly remain unexplored. Here we found Aspergillus nidulans that vezatin homolog VezA is important assembly. affects microtubule plus-end accumulation of dynein before adapter-mediated activation, two processes both need dynactin. The contains multiple components including an Arp1 (actin-related protein 1) mini-filament associated with a pointed-end sub-complex. physically interacts either directly or indirectly via its Loss causes defect integrity, most likely by affecting connection between Using various mutants, further revealed must be highly coordinated. Together, these results shed new light on vivo.

Язык: Английский

Development of near-isogenic line of dwarf gene Cldw-1 and transcriptome analysis in watermelon (Citrullus lanatus) DOI Creative Commons

Minjuan Zhang,

Wenkai Yan, Mengyuan Yan

и другие.

Scientia Horticulturae, Год журнала: 2025, Номер 343, С. 114065 - 114065

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Dynactin knockdown leads to synuclein aggregation by blocking autophagy in a zebrafish model of Parkinson's disease DOI Creative Commons

Yongmei Wu,

Qiang Guo,

Jinfan Gan

и другие.

Brazilian Journal of Medical and Biological Research, Год журнала: 2025, Номер 58

Опубликована: Янв. 1, 2025

Axons of dopaminergic neurons projecting from substantia nigra to striatum are severely affected in the early stage Parkinson's disease (PD), with axonal degeneration preceding loss cell bodies. Our previous study indicated that dysfunctional retrograde transport could lead death resulting PD (10.1111/j.1471-4159.2008.05526.x). However, dynein, as main molecule involved transport, was not affected. This aimed verify hypothesis dynactin rather than dynein may be one key factors PD. Dynactin morpholino used inhibit expression transgenic (Vmat2:GFP) zebrafish, a significant decrease diencephalon dopamine and synuclein aggregation basal plate region. In SH-SY5Y line, dynactin-siRNA knockdown resulted shifting dispersed distribution concentration synapses cytoplasm near axons, fusion rate decreased, especially which blocked α-synuclein autophagy flow. results linked gene dysfunction microtubule system, suggesting contributing

Язык: Английский

Процитировано

0
CCSer2 gates dynein activity at the cell periphery DOI
Juliana Zang, Daytan Gibson, Ann-Marie Zheng

и другие.

The Journal of Cell Biology, Год журнала: 2025, Номер 224(6)

Опубликована: Апрель 22, 2025

Cytoplasmic dynein-1 (dynein) is a microtubule-associated, minus end–directed motor that traffics hundreds of different cargos. Dynein must discriminate between cargos and traffic them at the appropriate time from correct cellular region. How dynein’s trafficking activity regulated in or space remains poorly understood. Here, we identify CCSer2 as first known protein to gate dynein spatial dimension. promotes migration developing zebrafish primordium cells, macrophages, cultured human cells by facilitating are acted on peripherally localized dynein. Our data suggest disfavors interaction its regulator Ndel1 cell edge, resulting activation. These findings support model where specificity achieved localization proteins trigger Ndel1’s release We propose defines broader class activate distinct microenvironments via regulating Ndel1–dynein interaction.

Язык: Английский

Процитировано

0
Multiple steps of dynein activation by Lis1 visualized by cryo-EM DOI Creative Commons
Agnieszka A. Kendrick, Kendrick H V Nguyen, Wen Ma

и другие.

Nature Structural & Molecular Biology, Год журнала: 2025, Номер unknown

Опубликована: Май 23, 2025

Abstract Cytoplasmic dynein-1 (dynein) is an essential molecular motor controlled in part by autoinhibition. Lis1, a key dynein regulator mutated the neurodevelopmental disease lissencephaly, plays role activation. We recently identified structure of partially autoinhibited bound to which suggests intermediate state dynein’s activation pathway. However, other structural information needed fully understand how Lis1 activates dynein. Here, we used cryo-EM and yeast incubated with ATP at different time points reveal conformations that propose represent additional states solved 16 high-resolution structures, including 7 distinct dynein–Lis1 structures from same sample. Our data support model relieves autoinhibition increasing its basal hydrolysis rate promoting compatible complex assembly motility. Together, this analysis advances our understanding contribution process.

Язык: Английский

Процитировано

0
Function of manchette and intra-manchette transport in spermatogenesis and male fertility DOI Creative Commons
Tingting Gao, Yang Liu, Jinghong Li

и другие.

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Май 29, 2025

The manchette is a transient skirt-like structure consisting of microtubules (MTs) and filamentous actin (F-actin) surrounding the elongating sperm head during spermiogenesis. It pivotal in shaping controlled by acrosome-acroplaxome-manchette complex, acrosome formation, flagellar assembly microtubular-based protein delivery. Defects frequently lead to teratozoospermia concomitant with oligozoospermia asthenozoospermia, but pathogenic mechanism underlying function its role male infertility remain poorly understood. In this review, we systematically described disassembly manchette, intra-manchette transport (IMT) regulatory model, IMT regulating spermatogenesis; summarized research progress manchette-related genes related infertility; listed proteins knockout mouse models clinical cases, which provide theoretical basis for an in-depth understanding molecular involved spermatogenesis fertility potentially developing treatments reproductive disorders.

Язык: Английский

Процитировано

0
Structural and functional insights into activation and regulation of the dynein-dynactin-NuMA complex DOI Creative Commons

Merve Aslan,

Ennio d’Amico, Nathan Cho

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 29, 2024

Abstract During cell division, NuMA orchestrates the focusing of microtubule minus-ends in spindle poles and cortical force generation on astral microtubules by interacting with dynein motors, microtubules, other cellular factors. Here we used vitro reconstitution, cryo-electron microscopy, live imaging to understand mechanism regulation NuMA. We determined structure processive dynein/dynactin/NuMA complex (DDN) showed that N-terminus drives motility facilitates dynein-mediated transport cells. The C-terminus directly binds suppresses dynamics minus-end. Full-length is autoinhibited, but mitotically phosphorylated activates interphase Together dynein, activated full-length focuses into aster-like structures. binding protein LGN results preferential plus-end. These provide critical insights activation for their functions body cortex.

Язык: Английский

Процитировано

2
The intracellular bacteriumOrientia tsutsugamushihijacks the adaptor protein BICD2 for dynein-based motility DOI Creative Commons
Giulia Manigrasso, Kittirat Saharat, Chitrasak Kullapanich

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 11, 2024

ABSTRACT The intracellular bacterium Orientia tsutsugamushi relies on the microtubule cytoskeleton and motor protein dynein to traffic perinuclear region within infected cells. However, it remains unclear how is coupled machinery transport regulated. Here, we discover that O. uses its autotransporter ScaC recruit adaptor BICD2 bacterial surface. We show sufficient engage dynein-based motility in absence of other proteins required for efficient movement during infection. Using TIRF single-molecule assays, demonstrate induces adopt an open conformation which activates assembly dynein-dynactin complexes. Our results reveal a novel role infection provide mechanistic insights into life cycle important human pathogen.

Язык: Английский

Процитировано

1
An initial HOPS-mediated fusion event is critical for autophagosome transport initiation from the axon terminal DOI

Serena R. Wisner,

Madison Chlebowski,

Amrita Mandal

и другие.

Autophagy, Год журнала: 2024, Номер 20(10), С. 2275 - 2296

Опубликована: Июнь 20, 2024

In neurons, macroautophagy/autophagy is a frequent and critical process. the axon, autophagy begins in axon terminal, where most nascent autophagosomes form. After formation, must initiate transport to exit terminal move toward cell body via retrograde transport. During these mature through repetitive fusion events. Complete lysosomal cargo degradation occurs largely body. The precipitating events stimulate autophagosome have been debated but their importance clear: disrupting neuronal or detrimental health function. We identified HOPS complex as essential for early maturation consequent initiation of from terminal. yeast mammalian cells, controls between late endosomes with lysosomes. Using zebrafish strains loss-of-function mutations

Язык: Английский

Процитировано

1
Systems mapping of bidirectional endosomal transport through the crowded cell DOI Creative Commons
Marlieke L.M. Jongsma,

Nina Bakker,

Lenard M. Voortman

и другие.

Current Biology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

1
Cargo adaptor identity controls the mechanism and kinetics of dynein activation DOI Creative Commons
John P. Gillies, Saffron R. Little, William O. Hancock

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 11, 2024

Abstract Cytoplasmic dynein-1 (dynein), the primary retrograde motor in most eukaryotes, supports movement of hundreds distinct cargos, each with specific trafficking requirements. To achieve this functional diversity, dynein must bind to multi-subunit complex dynactin and one a family cargo adaptors be converted into an active, processive complex. Very little is known about dynamic processes that promote formation delineate kinetic steps lead activation, we developed single-molecule fluorescence assay visualize real-time dynein-dynactin-adaptor complexes vitro. We found independently rather than cooperatively. also different assembly dramatically kinetics, which results occurring via pathways. Despite differences association rates or mechanism assembly, all tested can generate population tripartite are very stable. Our work provides model for how modulating kinetics binding harnessed differential activation reveals new facet diversity motor.

Язык: Английский

Процитировано

1