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

Molecular Motors in Myelination and Their Misregulation in Disease DOI Creative Commons
Daniel José Barbosa, Cátia Carvalho, Inês Costa

и другие.

Molecular Neurobiology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 31, 2024

Abstract Molecular motors are cellular components involved in the intracellular transport of organelles and materials to ensure cell homeostasis. This is particularly relevant neurons, where synaptic synthesized soma need travel over long distances their destination. They can walk on microtubules (kinesins dyneins) or actin filaments (myosins), major cytoskeleton. While kinesins mostly perform anterograde toward plus ends located distally processes, cytoplasmic dyneins allow retrograde flux cargo minus at soma. Axon myelination represents a aspect neuronal maturation essential for function, as it speeds up transmission electrical signals. Increasing evidence supports role molecular homeostatic control myelination. includes trafficking myelin along processes myelinating cells local regulation pathways that axon wrapping. Dysfunctional machinery has therefore been linked several brain pathologies, including demyelinating diseases. These disorders include broad spectrum conditions characterized by pathological demyelination axons within nervous system, ultimately leading axonal degeneration death, with multiple sclerosis representing most prevalent studied condition. review highlights involvement It also discusses studies have yielded insights into dysfunctional activity pathophysiology sclerosis.

Язык: Английский

Процитировано

1

CDR2 is a dynein adaptor recruited by kinectin to regulate ER sheet organization DOI Creative Commons
Vanessa Teixeira, Kashish Singh, José B. Gama

и другие.

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

Опубликована: Ноя. 6, 2024

ABSTRACT The endoplasmic reticulum (ER) relies on the microtubule cytoskeleton for distribution and re-modelling of its extended membrane network, but how microtubule-based motors contribute to ER organization remains unclear. Using biochemical cell-based assays, we identify cerebellar degeneration-related protein 2 (CDR2) paralog CDR2-like (CDR2L), onconeural antigens with poorly understood functions, as adaptors cytoplasmic dynein-1 (dynein). We demonstrate that CDR2 is recruited by integral kinectin (KTN1) double knockout CDR2L enhances KTN1-dependent sheet stacking, reversal which exogenous requires dynein-binding CC1 box motif. Exogenous expression additionally promotes box-dependent clustering sheets near centrosomes. competes eEF1Bβ subunit translation elongation factor 1 binding KTN1, knockdown increases endogenous levels sheets, inducing their centrosome-proximal clustering. Our study describes a novel molecular pathway implicates dynein in may be involved pathogenesis paraneoplastic degeneration.

Язык: Английский

Процитировано

1

A nucleotide code governs Lis1's ability to relieve dynein autoinhibition DOI Open Access

Indigo C. Geohring,

Pengxin Chai,

Bharat Ramasubramanian Iyer

и другие.

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

Опубликована: Дек. 30, 2024

Dynein-1 is a microtubule motor responsible for the transport of cytoplasmic cargoes. Activation motility requires it first overcome an autoinhibited state prior to its assembly with dynactin and cargo adaptor. Studies suggest that Lis1 may relieve dynein’s state. However, evidence this mechanism lacking. We set out determine rules governing dynein-Lis1 binding, which reveals their binding affinity regulated by nucleotide-bound states each three nucleotide-binding pockets within dynein domain. also find distinct nucleotide ‘codes’ coordinate stoichiometry impacting at two different sites Electron microscopy 1 Lis1:1 complex directly promotes open, uninhibited conformational dynein, whereas 2:1 resembles Cryo-EM analysis structural basis opening relies on interactions linker

Язык: Английский

Процитировано

1

VezA/vezatin facilitates proper assembly of the dynactin complex in vivo DOI Open Access
Jun Zhang, Rongde Qiu,

Sean Xie

и другие.

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

Опубликована: Апрель 20, 2024

Abstract 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

Процитировано

0

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

Процитировано

0