Vibrator and PI4KIIIα govern neuroblast polarity by anchoring non-muscle myosin II

Author:

Koe Chwee Tat1ORCID,Tan Ye Sing1,Lönnfors Max2,Hur Seong Kwon2,Low Christine Siok Lan3,Zhang Yingjie14,Kanchanawong Pakorn35,Bankaitis Vytas A2,Wang Hongyan146ORCID

Affiliation:

1. Neuroscience and Behavioral Disorders Programme, Duke-NUS Medical School, Singapore, Singapore

2. Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, United States

3. Mechanobiology Institute, National University of Singapore, Singapore, Singapore

4. NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore

5. Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore

6. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

Abstract

A central feature of most stem cells is the ability to self-renew and undergo differentiation via asymmetric division. However, during asymmetric division the role of phosphatidylinositol (PI) lipids and their regulators is not well established. Here, we show that the sole type I PI transfer protein, Vibrator, controls asymmetric division of Drosophilaneural stem cells (NSCs) by physically anchoring myosin II regulatory light chain, Sqh, to the NSC cortex. Depletion of vib or disruption of its lipid binding and transfer activities disrupts NSC polarity. We propose that Vib stimulates PI4KIIIα to promote synthesis of a plasma membrane pool of phosphatidylinositol 4-phosphate [PI(4)P] that, in turn, binds and anchors myosin to the NSC cortex. Remarkably, Sqh also binds to PI(4)P in vitro and both Vib and Sqh mediate plasma membrane localization of PI(4)P in NSCs. Thus, reciprocal regulation between Myosin and PI(4)P likely governs asymmetric division of NSCs.

Funder

Ministry of Education - Singapore

National Institutes of Health

Welch Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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