A sensitised RNAi screen reveals a ch-TOG genetic interaction network required for spindle assembly

نویسندگان

  • Alexis R. Barr
  • Chris Bakal
چکیده

How multiple spindle assembly pathways are integrated to drive bipolar spindle assembly is poorly understood. We performed an image-based double RNAi screen to identify genes encoding Microtubule-Associated Proteins (MAPs) that interact with the highly conserved ch-TOG gene to regulate bipolar spindle assembly in human cells. We identified a ch-TOG centred network of genetic interactions which promotes centrosome-mediated microtubule polymerisation, leading to the incorporation of microtubules polymerised by all pathways into a bipolar structure [corrected]. Our genetic screen also reveals that ch-TOG maintains a dynamic microtubule population, in part, through modulating HSET activity. ch-TOG ensures that spindle assembly is robust to perturbation but sufficiently dynamic such that spindles can explore a diverse shape space in search of structures that can align chromosomes.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Erratum: A sensitised RNAi screen reveals a ch-TOG genetic interaction network required for spindle assembly

In the original version of this Article, the Abstract contains a typographical error. " We identified a ch-TOG centred network of genetic interactions which promotes ensures centrosome-mediated microtubule polymerisation, leading to the incorporation of microtubules polym-erised by all pathways into a bipolar structure. " should read: " We identified a ch-TOG centred network of genetic interact...

متن کامل

Hsp72 is targeted to the mitotic spindle by Nek6 to promote K-fiber assembly and mitotic progression

Hsp70 proteins represent a family of chaperones that regulate cellular homeostasis and are required for cancer cell survival. However, their function and regulation in mitosis remain unknown. In this paper, we show that the major inducible cytoplasmic Hsp70 isoform, Hsp72, is required for assembly of a robust bipolar spindle capable of efficient chromosome congression. Mechanistically, Hsp72 as...

متن کامل

Coordination of adjacent domains mediates TACC3–ch-TOG–clathrin assembly and mitotic spindle binding

A complex of transforming acidic coiled-coil protein 3 (TACC3), colonic and hepatic tumor overexpressed gene (ch-TOG), and clathrin has been implicated in mitotic spindle assembly and in the stabilization of kinetochore fibers by cross-linking microtubules. It is unclear how this complex binds microtubules and how the proteins in the complex interact with one another. TACC3 and clathrin have ea...

متن کامل

TACC3–ch-TOG track the growing tips of microtubules independently of clathrin and Aurora-A phosphorylation

The interaction between TACC3 (transforming acidic coiled coil protein 3) and the microtubule polymerase ch-TOG (colonic, hepatic tumor overexpressed gene) is evolutionarily conserved. Loading of TACC3-ch-TOG onto mitotic spindle microtubules requires the phosphorylation of TACC3 by Aurora-A kinase and the subsequent interaction of TACC3 with clathrin to form a microtubule-binding surface. Rece...

متن کامل

The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells.

The ch-TOG/XMAP215 family of proteins bind directly to microtubules and appear to play an essential role in stabilizing spindle microtubules. These proteins stabilize microtubules mainly by influencing microtubule plus-end dynamics, yet, in vivo, they are all strongly concentrated at spindle poles, where the minus ends of the microtubules are concentrated. In Drosophila embryos, the centrosomal...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2015