Reconstitution of Dynein/Dynactin Transport Using Recombinant Dynein

Lau, C.K.

doi:10.1007/978-1-0716-2958-1_9

Cited by 2 publications

(2 citation statements)

References 19 publications

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“…Motility chambers were prepared as previously described 73 . Briefly, two strips of double-sided tape were applied to a glass slide (epredia ground 90º frosted, BS7011/2 1.0-1.2 mm) at ~5 mm apart.…”

Section: Methodsmentioning

confidence: 99%

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KIF1C activates and extends dynein movement through the FHF cargo adaptor

Ali,

Zwetsloot,

Stone

et al. 2023

Preprint

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Cellular cargos move bidirectionally on microtubules due to the presence of opposite polarity motors dynein and kinesin. Many studies show these motors are co-dependent, whereby one requires the activity of the other, although the mechanism is unknown. Here, using in vitro motility assays, we show that the kinesin-3 KIF1C acts both as an activator and a processivity factor for dynein. Activation only requires a fragment of the non-motor tail of KIF1C (KIF1C-stalk) to bind the cargo adaptor HOOK3. Cryo-EM, crosslinking mass spectrometry and AlphaFold2 predictions reveal this binding site to be separate from that of two constitutive factors (FTS and FHIP), which link HOOK3 to small G-proteins on cargos. We provide a structural model for how the FTS-HOOK3-FHIP1B (FHF) complex is auto-inhibited and explain how the KIF1C-stalk relieves this inhibition. Collectively, our work provides a molecular explanation for co-dependency by revealing that the mutual activation of dynein and kinesin is mediated through their shared adaptor. Many adaptors bind both dynein and kinesins, suggesting this mechanism could be generalised to other bidirectional complexes.

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Section: Methodsmentioning

confidence: 99%

“…Coverslips were exposed to plasma for 3 minutes with a setup of 75% Argon and 25% Oxygen at 100% power. Motility chambers were prepared as previously described 73 . Briefly, two strips of double-sided tape were applied to a glass slide (epredia ground 90º frosted, BS7011/2 1.0-1.2 mm) at ~5 mm apart.…”

Section: Alphafold Predictionsmentioning

confidence: 99%

KIF1C activates and extends dynein movement through the FHF cargo adaptor

Ali,

Zwetsloot,

Stone

et al. 2023

Preprint

View full text Add to dashboard Cite

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Cargo specificity, regulation, and therapeutic potential of cytoplasmic dynein

Park,

Jeon,

Hwang

et al. 2024

Exp Mol Med

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Intracellular retrograde transport in eukaryotic cells relies exclusively on the molecular motor cytoplasmic dynein 1. Unlike its counterpart, kinesin, dynein has a single isoform, which raises questions about its cargo specificity and regulatory mechanisms. The precision of dynein-mediated cargo transport is governed by a multitude of factors, including temperature, phosphorylation, the microtubule track, and interactions with a family of activating adaptor proteins. Activating adaptors are of particular importance because they not only activate the unidirectional motility of the motor but also connect a diverse array of cargoes with the dynein motor. Therefore, it is unsurprising that dysregulation of the dynein-activating adaptor transport machinery can lead to diseases such as spinal muscular atrophy, lower extremity, and dominant. Here, we discuss dynein motor motility within cells and in in vitro, and we present several methodologies employed to track the motion of the motor. We highlight several newly identified activating adaptors and their roles in regulating dynein. Finally, we explore the potential therapeutic applications of manipulating dynein transport to address diseases linked to dynein malfunction.

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Reconstitution of Dynein/Dynactin Transport Using Recombinant Dynein

Cited by 2 publications

References 19 publications

KIF1C activates and extends dynein movement through the FHF cargo adaptor

KIF1C activates and extends dynein movement through the FHF cargo adaptor

Cargo specificity, regulation, and therapeutic potential of cytoplasmic dynein

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