Pak1 kinase controls cell shape through ribonucleoprotein granules.

Joseph O Magliozzi,James B Moseley

doi:10.7554/elife.67648

Abstract

Fission yeast cells maintain a rod shape due to conserved signaling pathways that organize the cytoskeleton for polarized growth. We discovered a mechanism linking the conserved protein kinase Pak1 with cell shape through the RNA-binding protein Sts5. Pak1 (also called Shk1 and Orb2) prevents Sts5 association with P bodies by directly phosphorylating its intrinsically disordered region (IDR). Pak1 and the cell polarity kinase Orb6 both phosphorylate the Sts5 IDR but at distinct residues. Mutations preventing phosphorylation in the Sts5 IDR cause increased P body formation and defects in cell shape and polarity. Unexpectedly, when cells encounter glucose starvation, PKA signaling triggers Pak1 recruitment to stress granules with Sts5. Through retargeting experiments, we reveal that Pak1 localizes to stress granules to promote rapid dissolution of Sts5 upon glucose addition. Our work reveals a new role for Pak1 in regulating cell shape through ribonucleoprotein granules during normal and stressed growth conditions.

Highlights

Cell polarity signaling networks determine cell morphology by controlling growth machinery in time and space
S261 and S264 reside in the Sts5 intrinsically disordered region (IDR), which mediates its localization to RNP granules (Chen et al, 2019; Nuñez et al, 2016; Toda et al, 1996; Vaggi et al, 2012)
Orb6 phosphorylates S86 in the Sts5 IDR (Chen et al, 2019), while we have shown that Pak1 directly phosphorylates S261

Summary

Introduction

Cell polarity signaling networks determine cell morphology by controlling growth machinery in time and space. Following activation by small GTPases like Cdc, PAKs function in regulating the cytoskeleton and MAPK pathways, and PAK dysregulation is associated with multiple human diseases. The functions of PAKs in cell morphology and signaling are conserved in a wide range of cell types and organisms including yeast and humans (Hofmann et al, 2004). This conservation is demonstrated by the finding that expression of human PAK1 suppresses defects associated with loss of the PAK Ste in budding yeast (Brown et al, 1996). Full understanding of PAK function in cell polarity and proliferation requires identification of noncanonical substrates and functions for PAK-family proteins

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