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Published on: July 16, 2018
Membrane bleb: A seesaw game of two small GTPases
Junichi Ikenouchi1,2,3, Kana Aoki1
1a Department of Biology, Faculty of Sciences , Kyushu University , Fukuoka , Japan.
Abstract:
The plasma membrane is generally associated with underling actin cytoskeleton. When the plasma membrane detaches from actin filaments, it is expanded by the intracellular pressure and the spherical membrane protrusion which lacks underlying actin cortex, termed bleb, is formed. Bleb is widely used for migration across species; however, the molecular mechanism underlying membrane blebbing remains largely unknown. Our recent study revealed that 2 small GTPases, Rnd3 and RhoA, are important regulators of membrane blebbing. In the expanding blebs, Rnd3 is recruited to the plasma membrane and inhibits RhoA activity by activating RhoGAP. On the other hand, RhoA is activated at the retracting membrane and removes Rnd3 from plasma membrane by the activity of ROCK (Rho-associated protein kinase). ROCK is also important for the rapid reassembly of actin cortex and retraction of membrane blebs by activating Ezrin. We propose that a Rnd3 and RhoA cycle underlies the core machinery of continuous membrane blebbing.
Insights
Membrane blebbing, essential for cell migration, is regulated by a cycle of Rnd3 and RhoA GTPases. This Rnd3-RhoA cycle controls the formation and retraction of cellular blebs.
Area of Science:
- Cell biology
- Molecular and cell biology
Background:
- The plasma membrane interacts with the actin cytoskeleton.
- Membrane blebs are spherical protrusions formed when the plasma membrane detaches from the actin cortex.
- Blebs are crucial for cell migration but their molecular mechanisms are not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms regulating membrane blebbing.
- To identify key regulators of bleb formation and retraction.
Main Methods:
- Investigated the roles of small GTPases Rnd3 and RhoA in membrane blebbing.
- Examined the interaction between Rnd3, RhoA, RhoGAP, ROCK (Rho-associated protein kinase), and Ezrin during blebbing.
Main Results:
- Rnd3 inhibits RhoA activity by activating RhoGAP in expanding blebs.
- RhoA is activated at retracting membranes, removing Rnd3 via ROCK activity.
- ROCK promotes actin cortex reassembly and bleb retraction by activating Ezrin.
Conclusions:
- A Rnd3 and RhoA cycle is proposed as the core machinery for continuous membrane blebbing.
- This cycle involves dynamic regulation of GTPase activity and interactions with downstream effectors.
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