Dynactin Subunit p150Glued Is a Neuron-Specific Anti-Catastrophe Factor

Lazarus, Jacob E.; Moughamian, Armen J.; Tokito, Mariko; Holzbaur, Erika L.F.

doi:10.1371/journal.pbio.1001611

Cited by 93 publications

(99 citation statements)

References 65 publications

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“…Consistent with previous reports, light scattering was elevated: i.e., tubulin polymerization, in the presence of the dimerized CAP-Gly, with its basic extensions [p150(1-210) dimer] (Fig. S4A) (11). We also observed assisted tubulin polymerization with p150(1-144) fragments (Fig.…”

Section: Longitudinal Tubulin Oligomerization Is Induced By Cap-gly Psupporting

confidence: 92%

“…The masking of the acidic tails of tubulin by CAP-Gly plus basic patches causes the lateral association of tubulin. Moreover, previous reports established the ability of p150 fragments to promote the polymerization of microtubules (5,11). Therefore, we sought to correlate polymerization activity with the charge effects of various CAP-Gly fragments.…”

Section: Longitudinal Tubulin Oligomerization Is Induced By Cap-gly Pmentioning

confidence: 99%

“…Biophysical observations showed the ability of the +TIPs to promote microtubule polymerization (5,6,10). Recently, Lazarus et al (11) have demonstrated that the N-terminal dimeric portion of p150 glued is a neuron-specific anticatastrophe factor acting at the microtubule +end; a mutation in the CAP-Gly domain, which causes the lethal Perry syndrome, when introduced in their recombinant dimeric construct, abolishes the protective anticatastrophic depolymerization activity.…”

Section: P150mentioning

confidence: 99%

“…When tubulin oligomer formation was induced by the p150(1-210) dimer, which has the most prominent effect on tubulin polymerization (Fig. S4A) (11), large agglomerates of tubulin oligomers were visible in EM (Fig. 3).…”

Section: Longitudinal Tubulin Oligomerization Is Induced By Cap-gly Pmentioning

confidence: 99%

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Structural basis for the extended CAP-Gly domains of p150 ^glued binding to microtubules and the implication for tubulin dynamics

Wang

Crevenna

Kunze

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance This study presents a direct visualization of the microtubule-p150glued(CAP-Gly) complex by cryo-EM and seeks to describe the molecular mechanism of the control of tubulin dynamics by p150 CAP-Gly. It highlights the neutralization of the acidic tubulin surface by the basic extensions of CAP-Gly, resulting in the activation of tubulin polymerization. In the condition where the lateral association is impeded (i.e., at low temperature), the extended CAP-Gly domain induces tubulin dimers to connect longitudinally. The two directional modes of self-association of tubulin suggest a foundation for its dynamic behavior at the tip of microtubules and its regulation.

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Section: Longitudinal Tubulin Oligomerization Is Induced By Cap-gly Psupporting

confidence: 92%

Section: Longitudinal Tubulin Oligomerization Is Induced By Cap-gly Pmentioning

confidence: 99%

Section: P150mentioning

confidence: 99%

Section: Longitudinal Tubulin Oligomerization Is Induced By Cap-gly Pmentioning

confidence: 99%

See 2 more Smart Citations

Structural basis for the extended CAP-Gly domains of p150 ^glued binding to microtubules and the implication for tubulin dynamics

Wang

Crevenna

Kunze

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…The large subunit of the dynactin complex, p150 glued (DCTN1) is an evolutionarily conserved + TIP protein containing a N-terminal CAP-Gly domain mediating interaction with MT, and two C-terminal coiled-coil regions that are required for dimerization and interaction with the dynein intermediate chain and with dynactin shoulder (45,46). p150 glued promotes MT formation in vitro by catalyzing nucleation, increasing polymerization rate, and inhibiting catastrophe (47). The coiled-coil α-helical domain CC1B of p150 glued is necessary for its ability to enhance dynein processivity (48).…”

Section: Microtubule Plus-end Tracking Proteins (+ Tips)mentioning

confidence: 99%

Role of non-motile microtubule-associated proteins in virus trafficking

Portilho

Persson²,

Arhel

2016

Biomolecular Concepts

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Viruses are entirely dependent on their ability to infect a host cell in order to replicate. To reach their site of replication as rapidly and efficiently as possible following cell entry, many have evolved elaborate mechanisms to hijack the cellular transport machinery to propel themselves across the cytoplasm. Long-range movements have been shown to involve motor proteins along microtubules (MTs) and direct interactions between viral proteins and dynein and/or kinesin motors have been well described. Although less well-characterized, it is also becoming increasingly clear that non-motile microtubule-associated proteins (MAPs), including structural MAPs of the MAP1 and MAP2 families, and microtubule plus-end tracking proteins (+ TIPs), can also promote viral trafficking in infected cells, by mediating interaction of viruses with filaments and/or motor proteins, and modulating filament stability. Here we review our current knowledge on nonmotile MAPs, their role in the regulation of cytoskeletal dynamics and in viral trafficking during the early steps of infection.

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Tubulin mutations in neurodevelopmental disorders as a tool to decipher microtubule function

Fourel

Boscheron

2020

FEBS Letters

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Malformations of cortical development (MCDs) are a group of severe brain malformations associated with intellectual disability and refractory childhood epilepsy. Human missense heterozygous mutations in the 9 α‐tubulin and 10 β‐tubulin isoforms forming the heterodimers that assemble into microtubules (MTs) were found to cause MCDs. However, how a single mutated residue in a given tubulin isoform can perturb the entire microtubule population in a neuronal cell remains a crucial question. Here, we examined 85 MCD‐associated tubulin mutations occurring in TUBA1A, TUBB2, and TUBB3 and their location in a three‐dimensional (3D) microtubule cylinder. Mutations hitting residues exposed on the outer microtubule surface are likely to alter microtubule association with partners, while alteration of intradimer contacts may impair dimer stability and straightness. Other types of mutations are predicted to alter interdimer and lateral contacts, which are responsible for microtubule cohesion, rigidity, and dynamics. MCD‐associated tubulin mutations surprisingly fall into all categories, thus providing unexpected insights into how a single mutation may impair microtubule function and elicit dominant effects in neurons.

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Dynactin Subunit p150Glued Is a Neuron-Specific Anti-Catastrophe Factor

Abstract: The dynein partner dynactin not only binds to microtubules, but is found to potently influence microtubule dynamics in neurons.

Cited by 93 publications

References 65 publications

Structural basis for the extended CAP-Gly domains of p150 ^glued binding to microtubules and the implication for tubulin dynamics

Structural basis for the extended CAP-Gly domains of p150 ^glued binding to microtubules and the implication for tubulin dynamics

Role of non-motile microtubule-associated proteins in virus trafficking

Tubulin mutations in neurodevelopmental disorders as a tool to decipher microtubule function

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Dynactin Subunit p150Glued Is a Neuron-Specific Anti-Catastrophe Factor

Abstract: The dynein partner dynactin not only binds to microtubules, but is found to potently influence microtubule dynamics in neurons.

Cited by 93 publications

References 65 publications

Structural basis for the extended CAP-Gly domains of p150 glued binding to microtubules and the implication for tubulin dynamics

Structural basis for the extended CAP-Gly domains of p150 glued binding to microtubules and the implication for tubulin dynamics

Role of non-motile microtubule-associated proteins in virus trafficking

Tubulin mutations in neurodevelopmental disorders as a tool to decipher microtubule function

Contact Info

Product

Resources

About

Structural basis for the extended CAP-Gly domains of p150 ^glued binding to microtubules and the implication for tubulin dynamics

Structural basis for the extended CAP-Gly domains of p150 ^glued binding to microtubules and the implication for tubulin dynamics