University of Massachusetts Medical School Faculty Publications

Title

Identification of SIN pathway targets reveals mechanisms of crosstalk between NDR kinase pathways

UMMS Affiliation

Department of Microbiology and Physiological Systems; Program in Cell Dynamics

Date

2-18-2013

Document Type

Article

Medical Subject Headings

Cytokinesis; Cell Polarity; Signal Transduction

Disciplines

Cell Biology | Cellular and Molecular Physiology

Abstract

The septum initiation network (SIN) regulates multiple functions during late mitosis to ensure successful completion of cytokinesis in Schizosaccharomyces pombe. One mechanism by which the SIN promotes cytokinesis is by inhibiting a competing polarity pathway called the MOR, which is required for initiation of polarized growth following completion of cytokinesis. Mutual antagonism between the two NDR kinase pathways, SIN and MOR, is required to coordinate cytoskeletal rearrangements during the mitosis-interphase transition. To determine how the SIN regulates the MOR pathway, we developed a proteomics approach that allowed us to identify multiple substrates of the SIN effector kinase Sid2, including the MOR pathway components Nak1 kinase and an associated protein, Sog2. We show that Sid2 phosphorylation of Nak1 causes removal of Nak1 from the spindle pole bodies, which may both relieve Nak1 inhibition of the SIN and block MOR signaling by preventing interaction of Nak1 with the scaffold protein Mor2. Because the SIN and MOR are conserved in mammalian cells (Hippo and Ndr1/2 pathways, respectively), this work may provide important insight into how the activities of these essential pathways are coordinated.

Rights and Permissions

Citation: Curr Biol. 2013 Feb 18;23(4):333-8. doi: 10.1016/j.cub.2013.01.014. Link to article on publisher's site

Comments

First author Sneha Gupta is a doctoral student in the Interdisciplinary Graduate Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

Related Resources

Link to Article in PubMed

PubMed ID

23394829