Lgl antagonizes Par complex membrane association to enable neural stem cell asymmetric division

Area of Science:

• Cell Biology
• Developmental Biology
• Neuroscience

Background:

• The Par complex is crucial for establishing cell polarity in various animal cells.
• The tumor suppressor Lethal giant larvae (Lgl) is hypothesized to inhibit Par complex membrane binding.
• The localization of Lgl and the Par complex in metaphase Drosophila neural stem cells (NSCs) presents a paradox regarding Lgl's inhibitory role.

Purpose of the Study:

• To investigate how Lethal giant larvae (Lgl) controls Par complex localization in Drosophila neural stem cells (NSCs) when Lgl is not membrane-bound.
• To elucidate the dynamic relationship between Lgl and the Par complex during cell division.
• To understand the mechanism ensuring proper asymmetric cell division.

Main Methods:

• Live imaging of Drosophila neural stem cells (NSCs).
• Depletion of Lgl to observe effects on Par complex localization.
• Analysis of protein dynamics at the cell membrane during mitosis.

Main Results:

• Lethal giant larvae (Lgl) and atypical Protein Kinase C (aPKC) exhibit coordinated, opposing membrane dynamics: aPKC displaces Lgl at mitotic entry, and Lgl displaces aPKC at mitotic exit.
• In Lgl-depleted NSCs, residual aPKC persists on the membrane post-mitosis, disrupting Miranda polarization in subsequent divisions.
• Lgl is not essential for apical aPKC recruitment but ensures basal membrane clearance before mitosis.

Conclusions:

• A temporal mode of mutual antagonism exists between Lgl and the Par complex.
• This antagonism is critical for regulating Par complex localization and ensuring proper asymmetric cell division.
• Lgl's role in clearing aPKC from the basal membrane is vital for subsequent cell divisions.