# LZTS2 Negatively Regulates Centrosomal CEP135 Levels and Microtubule Nucleation

## TL;DR

This study shows that LZTS2, a tumor suppressor, controls microtubule formation at the centrosome by reducing levels of CEP135, a key microtubule nucleation factor.

## Contribution

The paper identifies a new role for LZTS2 as a negative regulator of centrosomal microtubule nucleation through CEP135.

## Key findings

- LZTS2 depletion increases microtubule nucleation at the centrosome.
- LZTS2 negatively regulates centrosomal levels of CEP135.
- LZTS2 depletion can partially rescue impaired microtubule nucleation caused by CEP135 knockdown.

## Abstract

The microtubule cytoskeleton is a fundamental functional component of the cell. In vertebrate proliferating cells, centrosomes are the primary microtubule organizing center (MTOC), and their dysregulation has been linked to genomic instability and cancer. LZTS2, a known tumor suppressor, localizes to centrosomes and regulates microtubule severing. However, whether LZTS2 regulates centrosome structure and/or its function in microtubule organization or ciliation remains unknown. Here, we investigate the function of LZTS2 at the centrosome. Through fluorescence and electron microscopy assays, we observed that LZTS2 knockdown does not affect centriole biogenesis or structure, nor ciliation. Importantly, we show that LZTS2 depletion increases microtubule nucleation at the centrosome. Moreover, LZTS2 negatively regulates centrosomal levels of CEP135. Notably, depletion of LZTS2 can partially rescue the impaired centrosome microtubule nucleation caused by CEP135 knockdown. Taken together, our findings reveal a novel role for LZTS2 as a negative regulator of CEP135 and centrosomal microtubule nucleation, providing a potential mechanistic link to its tumor suppressor function.