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.
Highlights
Understanding how neural stem cells divide asymmetrically is central for stem cell and cancer biology
We further demonstrate that depletion of PI4KIIIa(a PI4 kinase that is essential for PI(4)P synthesis) leads to Sqh delocalization and asymmetric division defects
Expression of phosphatidylinositol transfer proteins (PITPs) in vib133 fully rescued ectopic neuroblasts in b both type I (n = 100) and type II (n = 39) MARCM clones (Figure 1—figure supplement 1C). These results suggest that mammalian PITPs may play a conserved role in neuroblast homeostasis
Summary
Understanding how neural stem cells divide asymmetrically is central for stem cell and cancer biology. Each neuroblast divides asymmetrically to generate a selfrenewing neuroblast and a differentiating daughter cell It is the latter that produces neurons/glia (Doe, 2008). Asymmetric division of neuroblasts depends on the polarized distribution of proteins and their asymmetric segregation into different daughter cells. Apical proteins such as atypical protein kinase C (aPKC), Par-6 (Partitioning defective 6), Par-3/Bazooka (Baz), Inscuteable (Insc) and Partner of Inscuteable (Pins) control the localization of basal proteins, as well as the orientation of the mitotic spindle (Knoblich, 2010; Chang et al, 2012). Basal cell fate determinants Numb, Prospero (Pros), Brain tumor (Brat), and their adaptor proteins Partner of Numb (Pon) and Miranda (Mira) are critical for neuronal differentiation upon asymmetric segregation
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