A Tale of 12 Tails: Katanin Severing Activity Affected by Carboxy-Terminal Tail Sequences.

In cells, microtubule location, length, and dynamics are regulated by a host of microtubule-associated proteins and enzymes that read where to bind and act based on the microtubule "tubulin code," which is predominantly encoded in the tubulin carboxy-terminal tail (CTT). Katanin is a highly conserved AAA ATPase enzyme that binds to the tubulin CTTs to remove dimers and sever microtubules. We have previously demonstrated that short CTT peptides are able to inhibit katanin severing. Here, we examine the effects of CTT sequences on this inhibition activity. Specifically, we examine CTT sequences found in nature, alpha1A (TUBA1A), detyrosinated alpha1A, Δ2 alpha1A, beta5 (TUBB/TUBB5), beta2a (TUBB2A), beta3 (TUBB3), and beta4b (TUBB4b). We find that these natural CTTs have distinct abilities to inhibit, most noticeably beta3 CTT cannot inhibit katanin. Two non-native CTT tail constructs are also unable to inhibit, despite having 94% sequence identity with alpha1 or beta5 sequences. Surprisingly, we demonstrate that poly-E and poly-D peptides are capable of inhibiting katanin significantly. An analysis of the hydrophobicity of the CTT constructs indicates that more hydrophobic polypeptides are less inhibitory than more polar polypeptides. These experiments not only demonstrate inhibition, but also likely interaction and targeting of katanin to these various CTTs when they are part of a polymerized microtubule filament.

Katanin P60 and P80 in papillary thyroid carcinoma patients: Indicators for exacerbated tumor features and worse disease-free survival.

BACKGROUND: This study aimed to explore the clinical implications of katanin P60 and P80 (katanin P60/P80) regarding their correlations with clinicopathological features and survival profiles in papillary thyroid carcinoma (PTC) patients. METHODS: Tumor tissue and paired adjacent tissue specimens were obtained from 172 PTC patients who underwent lobectomy or thyroidectomy. Besides, immunohistochemistry assay and immunoreactive (IR) score (multiplying staining intensity score by density score) were used to determine katanin P60/P80 expressions. According to IR score (from 0 ~ 12), katanin P60/P80 expressions were classified as low (IR score 0 ~ 3) and high (IR score 4 ~ 12) expressions. RESULTS: Both katanin P60/P80 expressions were highly expressed in tumor tissue compared with adjacent tissue. Besides, tumor katanin P60 expression positively correlated with tumor katanin P80 expression. Tumor katanin P60 high expression correlated with larger tumor size, extrathyroidal invasion, advanced pT stage, pN stage, and pTNM stage, while no correlation of tumor katanin P60 expression with age or gender was observed; tumor katanin P80 high expression correlated with advanced pN stage and pTNM stage, whereas there was no correlation of tumor katanin P80 expression with age, gender, tumor size, extrathyroidal invasion, or pT stage. Furthermore, both tumor katanin P60/P80 high expressions correlated with shorter accumulating disease-free survival. As for overall survival (OS), neither tumor katanin P60 nor P80 expression correlated with OS. CONCLUSION: Katanin P60/P80 measurement might assist with tumor management and prognosis surveillance in PTC patients.

Microtubule­severing protein Katanin p60 ATPase­containing subunit A­like 1 is involved in pole­based spindle organization during mouse oocyte meiosis.

Microtubule­severing proteins (MTSPs) are a group of microtubule­associated proteins essential for multiple microtubule­related processes, including mitosis and meiosis. Katanin p60 ATPase­containing subunit A­like 1 (p60 katanin­like 1) is an MTSP that maintains the density of spindle microtubules at the poles in mitotic cells; however, to date, there have been no studies about its role in female meiosis. Using in vitro­matured (IVM) oocytes as a model, it was first revealed that p60 katanin­like 1 was predominant in the ovaries and oocytes, indicating its essential roles in oocyte meiosis. It was also revealed that p60 katanin­like 1 was concentrated at the spindle poles and co­localized and interacted with γ­tubulin, indicating that it may be involved in pole organization. Next, specific siRNA was used to deplete p60 katanin­like 1; the spindle organization was severely disrupted and characterized by an abnormal width:length ratio, multipolarity and extra aster microtubules out of the main spindles. Finally, it was determined that p60 katanin­like 1 knockdown retarded oocyte meiosis, reduced fertilization, and caused abnormal mitochondrial distribution. Collectively, these results indicated that p60 katanin­like 1 is essential for oocyte meiosis by ensuring the integrity of the spindle poles.