scholarly journals Dimerization is necessary for MIM-mediated membrane deformation and endocytosis

2012 ◽  
Vol 446 (3) ◽  
pp. 469-475 ◽  
Author(s):  
Meng Cao ◽  
Tailan Zhan ◽  
Min Ji ◽  
Xi Zhan
Keyword(s):  
Metastasis Suppressor ◽  
Intracellular Protein ◽  
High Potency ◽  
Membrane Deformation ◽  
Bar Domain ◽  
Membrane Protrusions ◽  
Metastasis Suppressor 1 ◽  
Intrinsic Capacity ◽  
Transferrin Uptake

MIM [missing in metastasis; also called MTSS1 (metastasis suppressor 1)] is an intracellular protein that binds to actin and cortactin and has an intrinsic capacity to sense and facilitate the formation of protruded membranous curvatures implicated in cell-ular polarization, mobilization and endocytosis. The N-terminal 250 amino acids of MIM undergo homodimerization and form a structural module with the characteristic of an I-BAR [inverse BAR (Bin/amphiphysin/Rvs)] domain. To discern the role of the dimeric configuration in the function of MIM, we designed several peptides able to interfere with MIM dimerization in a manner dependent upon their lengths. Overexpression of one of the peptides effectively abolished MIM-mediated membrane protrusions and transferrin uptake. However, a peptide with a high potency inhibiting MIM dimerization failed to affect its binding to actin and cortactin. Thus the results of the present study indicate that the dimeric configuration is essential for MIM-mediated membrane remodelling and serves as a proper target to develop antagonists specifically against an I-BAR-domain-containing protein.

scholarly journals Regulation of caveolae through cholesterol-depletion dependent tubulation by PACSIN2/Syndapin II

2020 ◽  
Author(s):  
Aini Gusmira Amir ◽  
Kazuhiro Takemura ◽  
Kyoko Hanawa-Suetsugu ◽  
Kayoko Oono-Yakura ◽  
Kazuma Yasuhara ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lipid Composition ◽  
Electrostatic Charge ◽  
Cholesterol Depletion ◽  
Membrane Deformation ◽  
Bar Domain ◽  
Caveolin 1 ◽  
Membrane Tubulation ◽  
Shaping Ability

AbstractThe membrane shaping ability of PACSIN2 via its FCH-BAR (F-BAR) domain has been shown to be essential for caveolar morphogenesis, presumably through the shaping of the caveolar neck. Caveolar membrane contains abundant levels of cholesterol. However, the role of cholesterol in PACSIN2-mediated membrane deformation remains unclear. We show that the binding of PACSIN2 to the membrane could be negatively regulated by the amount of cholesterol in the membrane. We prepared a reconstituted membrane based on the lipid composition of caveolae. The reconstituted membrane with cholesterol had a weaker affinity to the F-BAR domain of PACSIN2 than the membrane without cholesterol, presumably due to a decrease in electrostatic charge density. Consistently, the acute depletion of cholesterol from the plasma membrane resulted in the appearance of PACSIN2-localized tubules with caveolin-1 at their tips, suggesting that the presence of cholesterol inhibited the prominent membrane tubulation by PACSIN2. The tubules induced by PACSIN2 were suggested to be an intermediate of caveolae endocytosis. Consistently, the removal of caveolae from the plasma membrane upon cholesterol depletion was diminished in the cells deficient in PACSIN2. These data suggested that PACSIN2 mediated the caveolae internalization dependently on the amount of cholesterol at the plasma membrane, providing a possible mechanism for the cholesterol-dependent regulation of caveolae.

scholarly journals Role of Akt2 in regulation of metastasis suppressor 1 expression and colorectal cancer metastasis

Oncogene ◽  
2017 ◽  
Vol 36 (22) ◽  
pp. 3104-3118 ◽  
Author(s):  
E Agarwal ◽  
C M Robb ◽  
L M Smith ◽  
M G Brattain ◽  
J Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Metastasis Suppressor ◽  
Colorectal Cancer Metastasis ◽  
Metastasis Suppressor 1

scholarly journals Regulation of caveolae through cholesterol-depletion-dependent tubulation mediated by PACSIN2

2020 ◽  
Vol 133 (19) ◽  
pp. jcs246785 ◽  
Author(s):  
Aini Gusmira ◽  
Kazuhiro Takemura ◽  
Shin Yong Lee ◽  
Takehiko Inaba ◽  
Kyoko Hanawa-Suetsugu ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lipid Composition ◽  
Cholesterol Depletion ◽  
Membrane Deformation ◽  
Bar Domain ◽  
Caveolin 1 ◽  
Membrane Tubulation ◽  
Reconstituted Membranes ◽  
Shaping Ability

ABSTRACTThe membrane-shaping ability of PACSIN2 (also known as syndapin II), which is mediated by its F-BAR domain, has been shown to be essential for caveolar morphogenesis, presumably through the shaping of the caveolar neck. Caveolar membranes contain abundant cholesterol. However, the role of cholesterol in PACSIN2-mediated membrane deformation remains unclear. Here, we show that the binding of PACSIN2 to the membrane can be negatively regulated by cholesterol. We prepared reconstituted membranes based on the lipid composition of caveolae. The reconstituted membrane with cholesterol had a weaker affinity for the F-BAR domain of PACSIN2 than a membrane without cholesterol. Consistent with this, upon depletion of cholesterol from the plasma membrane, PACSIN2 localized at tubules that had caveolin-1 at their tips, suggesting that cholesterol inhibits membrane tubulation mediated by PACSIN2. The tubules induced by PACSIN2 could be representative of an intermediate of caveolae endocytosis. Consistent with this, the removal of caveolae from the plasma membrane upon cholesterol depletion was diminished in the PACSIN2-deficient cells. These data suggest that PACSIN2-mediated caveolae internalization is dependent on the amount of cholesterol, providing a mechanism for cholesterol-dependent regulation of caveolae.This article has an associated First Person interview with the first author of the paper.

scholarly journals Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain–like mechanism

2007 ◽  
Vol 176 (7) ◽  
pp. 953-964 ◽  
Author(s):  
Pieta K. Mattila ◽  
Anette Pykäläinen ◽  
Juha Saarikangas ◽  
Ville O. Paavilainen ◽  
Helena Vihinen ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Membrane Curvature ◽  
Membrane Dynamics ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Tubular Structures ◽  
Membrane Deformation ◽  
Bar Domain ◽  
Membrane Protrusions ◽  
Induce Plasma

The actin cytoskeleton plays a fundamental role in various motile and morphogenetic processes involving membrane dynamics. We show that actin-binding proteins MIM (missing-in-metastasis) and IRSp53 directly bind PI(4,5)P2-rich membranes and deform them into tubular structures. This activity resides in the N-terminal IRSp53/MIM domain (IMD) of these proteins, which is structurally related to membrane-tubulating BAR (Bin/amphiphysin/Rvs) domains. We found that because of a difference in the geometry of the PI(4,5)P2-binding site, IMDs induce a membrane curvature opposite that of BAR domains and deform membranes by binding to the interior of the tubule. This explains why IMD proteins induce plasma membrane protrusions rather than invaginations. We also provide evidence that the membrane-deforming activity of IMDs, instead of the previously proposed F-actin–bundling or GTPase-binding activities, is critical for the induction of the filopodia/microspikes in cultured mammalian cells. Together, these data reveal that interplay between actin dynamics and a novel membrane-deformation activity promotes cell motility and morphogenesis.

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