Intersectin-2L Regulates Caveola Endocytosis Secondary to Cdc42-mediated Actin Polymerization

Klein, Irene; Predescu, Dan; Sharma, Tiffany; Knezevic, Ivana; Malik, Asrar B.; Predescu, Sanda

doi:10.1074/jbc.m109.035071

Cited by 52 publications

(54 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The supernatant (containing G-actin) was removed, and the pellet (containing F-actin) was resuspended in the same volume of buffer containing 15 mM HEPES, pH 7.5, 0.15 mM NaCl, 1% Triton X-100, 1% Na deoxycholate, 0.1% SDS, 10 mM EDTA, 1 mM DTT, 1 mM NaVO4, and protease inhibitors. Equal volumes of the fractions containing F and G actin and ϳ10 g protein were separated on SDS gels, and the bands corresponding to actin were identified on Western blots with an anti-actin antibody (Cytoskeleton) and standard chemiluminescence (24). Films were quantified using NIH Image J software.…”

Section: Methodsmentioning

confidence: 99%

Biophysical properties of normal and diseased renal glomeruli

Wyss

Henderson

Byfield

et al. 2011

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

The mechanical properties of tissues and cells including renal glomeruli are important determinants of their differentiated state, function, and responses to injury but are not well characterized or understood. Understanding glomerular mechanics is important for understanding renal diseases attributable to abnormal expression or assembly of structural proteins and abnormal hemodynamics. We use atomic force microscopy (AFM) and a new technique, capillary micromechanics, to measure the elastic properties of rat glomeruli. The Young's modulus of glomeruli was 2,500 Pa, and it was reduced to 1,100 Pa by cytochalasin and latunculin, and to 1,400 Pa by blebbistatin. Cytochalasin or latrunculin reduced the F/G actin ratios of glomeruli but did not disrupt their architecture. To assess glomerular biomechanics in disease, we measured the Young's moduli of glomeruli from two mouse models of primary glomerular disease, Col4a3−/− mice (Alport model) and Tg26HIV/nl mice (HIV-associated nephropathy model), at stages where glomerular injury was minimal by histopathology. Col4a3−/− mice express abnormal glomerular basement membrane proteins, and Tg26HIV/nl mouse podocytes have multiple abnormalities in morphology, adhesion, and cytoskeletal structure. In both models, the Young's modulus of the glomeruli was reduced by 30%. We find that glomeruli have specific and quantifiable biomechanical properties that are dependent on the state of the actin cytoskeleton and nonmuscle myosins. These properties may be altered early in disease and represent an important early component of disease. This increased deformability of glomeruli could directly contribute to disease by permitting increased distension with hemodynamic force or represent a mechanically inhospitable environment for glomerular cells.

show abstract

Section: Methodsmentioning

confidence: 99%

Biophysical properties of normal and diseased renal glomeruli

Wyss

Henderson

Byfield

et al. 2011

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…They share highly similar structures and functions (31). ITSN1 was involved in mitogenic signaling and regulated GTPase cascades, such as Cdc42 (32)(33)(34)(35). Furthermore, ITSN1 and Sos1 formed complexes to lead to Ras activation (32).…”

Section: Discussionmentioning

confidence: 99%

Human Intersectin 2 (ITSN2) binds to Eps8 protein and enhances its degradation

Ding

Yang²,

Zhou³

et al. 2012

BMB Reports

View full text Add to dashboard Cite

Participates in actin remodeling through Rac and receptor endocytosis via Rab5. Here, we used yeast two-hybrid system with Eps8 as bait to screen a human brain cDNA library. ITSN2 was identified as the novel binding factor of Eps8. The interaction between ITSN2 and Eps8 was demonstrated by the in vivo co-immunoprecipitation and colocalization assays and the in vitro GST pull-down assays. Furthermore, we mapped the interaction domains to the region between amino acids 260-306 of Eps8 and the coiled-coil domain of ITSN2. In addition, protein stability assays and immunofluorescence analysis showed ITSN2 overexpression induced the degradation of Eps8 proteins, which was markedly alleviated with the lysosome inhibitor NH4Cl treatment. Taken together, our results suggested ITSN2 interacts with Eps8 and stimulates the degradation of Eps8 proteins. [BMB reports 2012; 45(3): 183-188]

show abstract

“…Activation of N-WASP by Cdc42, in complex with the actin nucleation and elongation factor Arp2/3, binds amphipathic proteins (Bu et al, 2009;. Cdc42 and Rac1 also control actin remodeling, which is required for the formation of caveolae at the plasma membrane (Klein et al, 2009;de Kreuk et al, 2011). During CLIC-mediated endocytosis, actin remodeling is controlled by Cdc42 together with Arf1 (Doherty and Lundmark, 2009;Kumari and Mayor, 2008) (Table 1).…”

Section: Sculpting Of Membrane Invaginationsmentioning

confidence: 99%

Cell surface dynamics – how Rho GTPases orchestrate the interplay between the plasma membrane and the cortical cytoskeleton

Curtis

Meldolesi

2012

Journal of Cell Science

View full text Add to dashboard Cite

SummarySmall GTPases are known to regulate hundreds of cell functions. In particular, Rho family GTPases are master regulators of the cytoskeleton. By regulating actin nucleation complexes, Rho GTPases control changes in cell shape, including the extension and/or retraction of surface protrusions and invaginations. Protrusion and invagination of the plasma membrane also involves the interaction between the plasma membrane and the cortical cytoskeleton. This interplay between membranes and the cytoskeleton can lead to an increase or decrease in the plasma membrane surface area and its tension as a result of the fusion (exocytosis) or internalization (endocytosis) of membranous compartments, respectively. For a long time, the cytoskeleton and plasma membrane dynamics were investigated separately. However, studies from many laboratories have now revealed that Rho GTPases, their modulation of the cytoskeleton, and membrane traffic are closely connected during the dynamic remodeling of the cell surface. Arf-and Rab-dependent exocytosis of specific vesicles contributes to the targeting of Rho GTPases and their regulatory factors to discrete sites of the plasma membrane. Rho GTPases regulate the tethering of exocytic vesicles and modulate their subsequent fusion. They also have crucial roles in the different forms of endocytosis, where they participate in the sorting of membrane domains as well as the sculpting and sealing of membrane flasks and cups. Here, we discuss how cell surface dynamics depend on the orchestration of the cytoskeleton and the plasma membrane by Rho GTPases.

show abstract

Intersectin-2L Regulates Caveola Endocytosis Secondary to Cdc42-mediated Actin Polymerization

Cited by 52 publications

References 30 publications

Biophysical properties of normal and diseased renal glomeruli

Biophysical properties of normal and diseased renal glomeruli

Human Intersectin 2 (ITSN2) binds to Eps8 protein and enhances its degradation

Cell surface dynamics – how Rho GTPases orchestrate the interplay between the plasma membrane and the cortical cytoskeleton

Contact Info

Product

Resources

About