Structural and Molecular Basis for Katanin-Mediated Severing of Glutamylated Microtubules

Shin, Sang Chul; Im, Sun-Kyoung; Jang, Eun‐Hae; Jin, Kyeong Sik; Hur, Eun Mi; Kim, Eunice EunKyeong

doi:10.1016/j.celrep.2019.01.020

Cited by 61 publications

(61 citation statements)

References 63 publications

(94 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…concentrated Camsaps into the central lumen, where Camsaps stabilized the minus ends of the seeds to allow central MT elongation. As emerging evidence suggests that Wdr47, Camsaps, and Katanin also similarly impact neuronal polarization and axonal growth 14,15,17,40,41 , our findings indicate that the same pathway is used to properly generate and organize non-centrosomal MT arrays in polarized subcellular compartments such as the axon and motile cilium.…”

Section: Introductionsupporting

confidence: 59%

“…Nevertheless, no evidence to date suggests a localization of -tubulin in mammalian multicilia [61][62][63] . As Katanin is able to server curved MT lattices and MTs that are post-translationally modified (including poly-glutamylation abundant in peripheral MTs) 37,40,64,65 , we propose that it directly servers peripheral MTs to generate the seeds (Fig. 7g).…”

Section: Discussionmentioning

confidence: 99%

“…Our analyses on mutants indicate that their functions mainly depended on the minus-end stabilization activity ( Wdr47 targets Camsaps to direct the MT positioning. In addition to the CP formation, emerging clues of their corporative actions are reported in neurons 14,15,17,40,41,66 and epithelial cells 16,18,67 . Other non-centrosomal MT arrays requiring Camsaps [5][6][7] could involve Katanin and Wdr47 as well.…”

Section: S6a-c)mentioning

confidence: 99%

See 2 more Smart Citations

Wdr47, Camsaps, and Katanin cooperate to generate ciliary central microtubules

Líu

Zheng

Zhu

et al. 2020

Preprint

View full text Add to dashboard Cite

The axonemal central pair (CP) are non-centrosomal microtubules critical for planar ciliary beat. How they form, however, is poorly understood. Here, we show that mammalian CP formation requires cooperative activities of Katanin, Camsaps, and Wdr47. Katanin severs peripheral microtubules to produce central microtubule seeds in nascent cilia. Camsaps stabilize minus ends of the seeds to facilitate MT outgrowth, whereas Wdr47 concentrates Camsaps into the axonemal central lumen to properly position the central microtubules. Wdr47 deficiency in mouse multicilia results in complete loss of CP, rotatory beat, and primary ciliary dyskinesia. Overexpression of Camsaps induces central microtubules in Wdr47-/- ependymal cells but at the expense of low efficiency, abnormal numbers, and wrong location, whereas overexpression of a dominant inhibitor of Katanin impairs the CP formation. We propose that Wdr47, Camsaps, and Katanin constitute a general cooperative work team for the generation of non-centrosomal MT arrays in polarized subcellular compartments.

show abstract

Section: Introductionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: S6a-c)mentioning

confidence: 99%

See 1 more Smart Citation

Wdr47, Camsaps, and Katanin cooperate to generate ciliary central microtubules

Líu

Zheng

Zhu

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…tant for regulation of microtubule turnover and the recruitment of microtubule severing enzymes, such as katanin and spastin (16)(17)(18). Glycylation is primarily found on cilia, but the functional role of polyglycylation is not well-understood (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

C-terminal tail polyglycylation and polyglutamylation alter microtubule mechanical properties

Wall

Hart

Lee

et al. 2019

Preprint

View full text Add to dashboard Cite

Microtubules are biopolymers that perform diverse cellular functions. The regulation of microtubule behavior occurs in part through post-translational modification of both the ↵and -subunits of tubulin. One class of modifications is the heterogeneous addition of glycine and glutamate residues to the disordered C-terminal tails of tubulin. Due to their prevalence in stable, high stress cellular structures such as cilia, we sought to determine if these modifications alter the intrinsic sti ness of microtubules. Here we describe the purification and characterization of di erentially-modified pools of tubulin from Tetrahymena thermophila. We found that glycylation on the ↵-C-terminal tail is a key determinant of microtubule sti ness, but does not a ect the number of protofilaments incorporated into microtubules. We measured the dynamics of the tail peptide backbone using nuclear magnetic resonance spectroscopy. We found that the spin-spin relaxation rate (R 2 ) showed a pronounced decreased as a function of distance from the tubulin surface for the ↵-tubulin tail, indicating that the ↵-tubulin tail interacts with the dimer surface. This suggests that the interactions of the ↵-C-terminal tail with the tubulin body contributes to the sti ness of the assembled microtubule, providing insight into the mechanism by which glycylation and glutamylation can alter microtubule mechanical properties.SIGNIFICANCE Microtubules are regulated in part by post-translational modifications including the heterogeneous addition of glycine and glutamate residues to the C-terminal tails. By producing and characterizing di erentially-modified tubulin, this work provides insight into the molecular mechanisms of how these modifications alter intrinsic microtubule properties such as flexibility. These results have broader implications for mechanisms of how ciliary structures are able to function under high stress.

show abstract

“…Recent work has demonstrated that polyglutamylation induces microtubule severing by recruiting and honing katanin and spastin severing protein activity. [58][59][60] Additionally, paclitaxel treatment increases tubulin polyglutamylation within microtubules and we hypothesized that the increased polyglutamylation could sensitize microtubules to severing by spastin. 61 In a preliminary experiment, we measured the levels of tubulin polyglutamylation over time in synchronized A549 cells after release from a G1/S block.…”

Section: Discussionmentioning

confidence: 99%

Reorganization of paclitaxel-stabilized microtubule arrays at mitotic entry: roles of depolymerizing kinesins and severing proteins

Leung

Cassimeris

2019

Cancer Biology & Therapy

View full text Add to dashboard Cite

Paclitaxel is a widely used anti-cancer treatment that disrupts cell cycle progression by blocking cells in mitosis. The block at mitosis, with spindles assembled from short microtubules, is surprising given paclitaxel's microtubule stabilizing activity and the need to depolymerize long interphase microtubules prior to spindle formation. Cells must antagonize paclitaxel's microtubule stabilizing activity during a brief window of time at the transition from interphase to mitosis, allowing microtubule reorganization into a mitotic spindle, although the mechanism underlying microtubule depolymerization in the presence of paclitaxel has not been examined. Here we test the hypothesis that microtubule severing and/ or depolymerizing proteins active at mitotic entry are necessary to clear the interphase array in paclitaxel-treated cells and allow subsequent formation of mitotic spindles formed of short microtubules. A549 and LLC-PK1 cells treated with 30nM paclitaxel approximately 4 h prior to mitotic entry successfully progress through the G2/M transition by clearing the interphase microtubule array from the cell interior outward to the cell periphery, a spatial pattern of reorganization that differs from that of cells possessing dynamic microtubules. Depletion of kinesin-8s, KIF18A and/or KIF18B obstructed interphase microtubule clearing at mitotic entry in paclitaxel-treated cells, with KIF18B making the larger contribution. Of the severing proteins, depletion of spastin, but not katanin, reduced microtubule loss as cells entered mitosis in the presence of paclitaxel. These results support a model in which KIF18A, KIF18B, and spastin promote interphase microtubule array disassembly at mitotic entry and can overcome paclitaxel-induced microtubule stability specifically at the G2/M transition.

show abstract

Structural and Molecular Basis for Katanin-Mediated Severing of Glutamylated Microtubules

Cited by 61 publications

References 63 publications

Wdr47, Camsaps, and Katanin cooperate to generate ciliary central microtubules

Wdr47, Camsaps, and Katanin cooperate to generate ciliary central microtubules

C-terminal tail polyglycylation and polyglutamylation alter microtubule mechanical properties

Reorganization of paclitaxel-stabilized microtubule arrays at mitotic entry: roles of depolymerizing kinesins and severing proteins

Contact Info

Product

Resources

About