Mdp3 is a novel microtubule-binding protein that regulates microtubule assembly and stability

Sun, Xiaoou; Shi, Xingjuan; Liu, Min; Li, Dengwen; Zhang, Linlin; Liu, Xinqi; Zhou, Jun

doi:10.4161/cc.10.22.18106

Cited by 44 publications

(45 citation statements)

References 21 publications

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“…Strikingly, depletion of DDA3 or Mdp3 increased the level of Mdp3 or DDA3 in the complex, respectively. In agreement with previous findings (Sun et al, 2011), endogenous Mdp3 was localized to the mitotic spindle from prometaphase to anaphase (Fig. 1D) and colocalized with DDA3 at the spindle during metaphase (Fig.…”

Section: Results and Discussion Mdp3 Forms The Dda3 Complex During MIsupporting

confidence: 80%

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DDA3 and Mdp3 modulate Kif2a recruitment onto the mitotic spindle to control minus-end spindle dynamics

Kwon

Park

Song

et al. 2016

Journal of Cell Science

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Active turnover of spindle microtubules (MTs) for the formation of a bi-orientated spindle, chromosome congression and proper chromosome segregation is regulated by MT depolymerases such as the kinesin-13 family and the plus-end-tracking proteins (+TIPs). However, the control mechanisms underlying the spindle MT dynamics that are responsible for poleward flux at the minus end of MTs are poorly understood. Here, we show that Mdp3 (also known as MAP7D3) forms a complex with DDA3 (also known as PSRC1) and controls spindle dynamics at the minus end of MTs by inhibiting DDA3-mediated Kif2a recruitment to the spindle. Aberrant Kif2a activity at the minus end of spindle MTs in Mdp3-depleted cells decreased spindle stability and resulted in unaligned chromosomes in metaphase, lagging chromosomes in anaphase, and chromosome bridges in telophase and cytokinesis. Although they play opposing roles in minus-end MT dynamics, acting as an MT destabilizer and an MT stabilizer, respectively, DDA3 and Mdp3 did not affect the localization of each other. Thus, the DDA3 complex orchestrates MT dynamics at the MT minus end by fine-tuning the recruitment of Kif2a to regulate minus-end MT dynamics and poleward MT flux at the mitotic spindle.

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Section: Results and Discussion Mdp3 Forms The Dda3 Complex During MIsupporting

confidence: 80%

“…S1A). Although Mdp3 has been identified as a spindle-associated protein through proteomic analysis (Sauer et al, 2005;Sun et al, 2011), its mitotic function has not been characterized. Hence, we asked whether endogenous Mdp3 and DDA3 form a complex during the cell cycle.…”

Section: Results and Discussion Mdp3 Forms The Dda3 Complex During MImentioning

confidence: 99%

DDA3 and Mdp3 modulate Kif2a recruitment onto the mitotic spindle to control minus-end spindle dynamics

Kwon

Park

Song

et al. 2016

Journal of Cell Science

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“…Many microtubule-associated proteins (MAPs), such as Mdp3, Dysferlin, Furry, and MST2, are reported to increase microtubule stability by regulating MT acetylation. [40][41][42][43] Therefore, we propose that EWSR1 is a new MAP that can regulate MT acetylation in spindles, along with MT stability and density.…”

Section: Discussionmentioning

confidence: 99%

EWSR1 regulates mitosis by dynamically influencing microtubule acetylation

et al. 2016

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EWSR1, participating in transcription and splicing, has been identified as a translocation partner for various transcription factors, resulting in translocation, which in turn plays crucial roles in tumorigenesis. Recent studies have investigated the role of EWSR1 in mitosis. However, the effect of EWSR1 on mitosis is poorly understood. Here, we observed that depletion of EWSR1 resulted in cell cycle arrest in the mitotic phase, mainly due to an increase in the time from nuclear envelope breakdown to metaphase, resulting in a high percentage of unaligned chromosomes and multipolar spindles. We also demonstrated that EWSR1 is a spindle-associated protein that interacts with a-tubulin during mitosis. EWSR1 depletion increased the cold-sensitivity of spindle microtubules, and decreased the rate of spindle assembly. EWSR1 regulated the level of microtubule acetylation in the mitotic spindle; microtubule acetylation was rescued in EWSR1-depleted mitotic cells following suppression of HDAC6 activity by its specific inhibitor or siRNA treatment. In summary, these results suggest that EWSR1 regulates the acetylation of microtubules in a cell cycledependent manner through its dynamic location on spindle MTs, and may be a novel regulator for mitosis progress independent of its translocation.

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“…It was shown to promote the assembly and stability of microtubules in vitro as well as in cells [25], [26]. MAP7D3 has two potential coiled coil motifs at the N-terminus and it was shown that these coiled coil motifs constitute the microtubule binding region of the protein, although the effects of the microtubule binding region on microtubule polymerization and stability are not known [26]. Interestingly, the N-terminal conserved region has a common function in the proteins MAP7 and MAP7D3.…”

Section: Introductionmentioning

confidence: 99%

C-Terminal Region of MAP7 Domain Containing Protein 3 (MAP7D3) Promotes Microtubule Polymerization by Binding at the C-Terminal Tail of Tubulin

2014

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MAP7 domain containing protein 3 (MAP7D3), a newly identified microtubule associated protein, has been shown to promote microtubule assembly and stability. Its microtubule binding region has been reported to consist of two coiled coil motifs located at the N-terminus. It possesses a MAP7 domain near the C-terminus and belongs to the microtubule associated protein 7 (MAP7) family. The MAP7 domain of MAP7 protein has been shown to bind to kinesin-1; however, the role of MAP7 domain in MAP7D3 remains unknown. Based on the bioinformatics analysis of MAP7D3, we hypothesized that the MAP7 domain of MAP7D3 may have microtubule binding activity. Indeed, we found that MAP7 domain of MAP7D3 bound to microtubules as well as enhanced the assembly of microtubules in vitro. Interestingly, a longer fragment MDCT that contained the MAP7 domain (MD) with the C-terminal tail (CT) of the protein promoted microtubule polymerization to a greater extent than MD and CT individually. MDCT stabilized microtubules against dilution induced disassembly. MDCT bound to reconstituted microtubules with an apparent dissociation constant of 3.0±0.5 µM. An immunostaining experiment showed that MDCT localized along the length of the preassembled microtubules. Competition experiments with tau indicated that MDCT shares its binding site on microtubules with tau. Further, we present evidence indicating that MDCT binds to the C-terminal tail of tubulin. In addition, MDCT could bind to tubulin in HeLa cell extract. Here, we report a microtubule binding region in the C-terminal region of MAP7D3 that may have a role in regulating microtubule assembly dynamics.

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Mdp3 is a novel microtubule-binding protein that regulates microtubule assembly and stability

Cited by 44 publications

References 21 publications

DDA3 and Mdp3 modulate Kif2a recruitment onto the mitotic spindle to control minus-end spindle dynamics

DDA3 and Mdp3 modulate Kif2a recruitment onto the mitotic spindle to control minus-end spindle dynamics

EWSR1 regulates mitosis by dynamically influencing microtubule acetylation

C-Terminal Region of MAP7 Domain Containing Protein 3 (MAP7D3) Promotes Microtubule Polymerization by Binding at the C-Terminal Tail of Tubulin

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