Neuroscience and Behavioral Disorders Programme, Duke-NUS Medical School, Singapore, Singapore
Ye Sing Tan
Neuroscience and Behavioral Disorders Programme, Duke-NUS Medical School, Singapore, Singapore
Max Lönnfors
Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, United States
Seong Kwon Hur
Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, United States
Christine Siok Lan Low
Mechanobiology Institute, National University of Singapore, Singapore, Singapore
Yingjie Zhang
Neuroscience and Behavioral Disorders Programme, Duke-NUS Medical School, Singapore, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore
Pakorn Kanchanawong
Mechanobiology Institute, National University of Singapore, Singapore, Singapore; Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore
Vytas A Bankaitis
Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, United States
Neuroscience and Behavioral Disorders Programme, Duke-NUS Medical School, Singapore, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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.
