The kinesin KIF21B participates in the cell surface delivery of γ2 subunit-containing GABAA receptors

Labonté, Dorthe; Thies, Edda; Kneussel, Matthias

doi:10.1016/j.ejcb.2014.07.007

Cited by 36 publications

(42 citation statements)

References 35 publications

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“…We show that KIF21B is highly processive, and together with its known function in MT-dependent transport (Labonte et al, 2014), also identify a role for KIF21B in regulating MT dynamics. Thus, similar to other kinesin-4 family members (Drummond, 2011; Walczak et al, 2013), KIF21B exerts dual functions as a processive motor and MT regulator.…”

Section: Discussionmentioning

confidence: 74%

“…Within neurons, KIF21B is present in axons and dendrites, with particular enrichment in growth cones of developing neurons (Huang and Banker, 2012; Marszalek et al, 1999). KIF21B binds E3 ubiquitin ligase TRIM3 (tripartite motif protein 3) to regulate GABA A receptor surface delivery (Labonte et al, 2014; Labonte et al, 2013). Micro-duplications in the chromosomal region 1q32.1, including the Kif21b gene, have been described in individuals with delayed motor and cognitive development (Olson et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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The Kinesin KIF21B Regulates Microtubule Dynamics and Is Essential for Neuronal Morphology, Synapse Function, and Learning and Memory

et al. 2016

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SUMMARY The kinesin KIF21B is implicated in several human neurological disorders including delayed cognitive development, yet it remains unclear how KIF21B dysfunction may contribute to pathology. One limitation is that relatively little is known about KIF21B-mediated physiological mechanisms. Here, we generated Kif21b knockout mice and used cellular assays to investigate the relevance of KIF21B in neuronal and in vivo function. We show that KIF21B is a processive motor, and identify an additional role for KIF21B in regulating microtubule dynamics. In neurons lacking KIF21B, microtubules grow more slowly and persistently, leading to tighter packing in dendrites. KIF21B-deficient neurons exhibit decreased dendritic arbor complexity and reduced spine density, which correlate with deficits in synaptic transmission. Consistent with these observations, KIF21B-null mice exhibit behavioral changes involving learning and memory deficits. Collectively, our study provides insight into the cellular function of KIF21B and the basis for cognitive decline resulting from KIF21B dysregulation.

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Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

The Kinesin KIF21B Regulates Microtubule Dynamics and Is Essential for Neuronal Morphology, Synapse Function, and Learning and Memory

et al. 2016

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“…ATG8s were originally implicated in membrane trafficking processes 53 . GABARAP family members facilitate transport of vesicular structures along microtubules 54, 55 to the plasma membrane, and here mediate the fusion of these vesicles with the plasma membrane 56–58 . Anticipating that GABARAPs are involved in the trafficking of Nef to the plasma membrane, we investigated whether Nef localizes with the GABARAPs in vesicular structures and whether expression of Nef and the ATG8 proteins lead to changes in their distribution patterns when compared with that of the patterns obtained for the individual factors.…”

Section: Resultsmentioning

confidence: 99%

Direct binding to GABARAP family members is essential for HIV-1 Nef plasma membrane localization

Boeske

Schwarten

et al. 2017

Sci Rep

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HIV-1 Nef is an important pathogenic factor for HIV/AIDS pathogenesis. Studies have shown that the association of Nef with the inner leaflet of the plasma membrane and with endocytic and perinuclear vesicles is essential for most activities of Nef. Using purified recombinant proteins in pull-down assays and by co-immunoprecipitation assays we demonstrate that Nef binds directly and specifically to all GABARAP family members, but not to LC3 family members. Based on nuclear magnetic resonance (NMR) experiments we showed that Nef binds to GABARAP via two surface exposed hydrophobic pockets. S53 and F62 of GABARAP were identified as key residues for the interaction with Nef. During live-cell fluorescence microscopy an accumulation of Nef and all GABARAP family members in vesicular structures throughout the cytoplasm and at the plasma membrane was observed. This plasma membrane accumulation was significantly reduced after knocking down GABARAP, GABARAPL1 and GABARAPL2 with respective siRNAs. We identified GABARAPs as the first known direct interaction partners of Nef that are essential for its plasma membrane localization.

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“…Furthermore, it has been demonstrated that KIF21B binds to the ubiquitin E3 ligase TRIM3, which can modulate the function of KIF21B (Labonté et al, 2013). The motor was also implicated in the surface delivery of GABA A receptors in neurons, but the interaction is likely indirect (Labonté et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

Kinesin-4 KIF21B is a potent microtubule pausing factor

Riel

Rai

Bianchi

et al. 2017

eLife

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Microtubules are dynamic polymers that in cells can grow, shrink or pause, but the factors that promote pausing are poorly understood. Here, we show that the mammalian kinesin-4 KIF21B is a processive motor that can accumulate at microtubule plus ends and induce pausing. A few KIF21B molecules are sufficient to induce strong growth inhibition of a microtubule plus end in vitro. This property depends on non-motor microtubule-binding domains located in the stalk region and the C-terminal WD40 domain. The WD40-containing KIF21B tail displays preference for a GTP-type over a GDP-type microtubule lattice and contributes to the interaction of KIF21B with microtubule plus ends. KIF21B also contains a motor-inhibiting domain that does not fully block the interaction of the protein with microtubules, but rather enhances its pause-inducing activity by preventing KIF21B detachment from microtubule tips. Thus, KIF21B combines microtubule-binding and regulatory activities that together constitute an autonomous microtubule pausing factor.DOI: http://dx.doi.org/10.7554/eLife.24746.001

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The kinesin KIF21B participates in the cell surface delivery of γ2 subunit-containing GABAA receptors

Cited by 36 publications

References 35 publications

The Kinesin KIF21B Regulates Microtubule Dynamics and Is Essential for Neuronal Morphology, Synapse Function, and Learning and Memory

The Kinesin KIF21B Regulates Microtubule Dynamics and Is Essential for Neuronal Morphology, Synapse Function, and Learning and Memory

Direct binding to GABARAP family members is essential for HIV-1 Nef plasma membrane localization

Kinesin-4 KIF21B is a potent microtubule pausing factor

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