Complex structures of Rsu1 and PINCH1 reveal a regulatory mechanism of the ILK/PINCH/Parvin complex for F-actin dynamics

Yang, Haibin; Lin, Leishu; Sun, Kang; Zhang, Ting; Chen, Wan; Li, Lianghui; Xie, Yuchen; Wu, Chuanyue; Wei, Zhiyi; Yu, Cong

doi:10.7554/elife.64395

Cited by 13 publications

(8 citation statements)

References 45 publications

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“…As in Pinch2 cKO nerves PI3K-AKT and PTEN signaling, known to drive myelin membrane growth (Harrington et al, 2010, Goebbels et al, 2010, Flores et al, 2008, Ishii et al, 2013 were not significantly affected, reduced RhoA activity could result in inhibition of actin nucleation via the Rho GTPase effectors Diaphonous-related formins (Kuhn and Geyer, 2014), ultimately leading to decrease of actin filaments and augmented membrane expansion and myelin wrapping. Of note, actin dynamics can also be controlled by Rsu1 protein , Gonzalez-Nieves et al, 2013, Yang et al, 2021 and Rsu1 transcript is reduced along OL development (Zhang et al, 2014) and in Pinch2 cKOs (our results).…”

Section: Discussionsupporting

confidence: 68%

Pinch2 is a novel regulator of myelination in the Central Nervous System

Faria

Vale-Silva

Fässler³

et al. 2022

Preprint

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The extensive morphological changes of oligodendrocytes during axon ensheathment and myelination involve assembly of the Ilk-Parvin-Pinch (IPP) heterotrimeric complex of proteins to relay essential mechanical and biochemical signals between integrins and the actin cytoskeleton. Binding of Pinch 1 and 2 isoforms to Ilk is mutually exclusive and allows the formation of distinct IPP complexes with specific signaling properties. Using tissue-specific conditional gene ablation in mice, we reveal an essential role for Pinch2 during central nervous system myelination. Unlike Pinch1-gene ablation, loss of Pinch2 in oligodendrocytes results in hypermyelination and in the formation of pathological myelin outfoldings in white matter regions. These structural changes concurred with inhibition of Rho GTPases RhoA and Cdc42 activities and phenocopied aspects of myelin pathology observed in corresponding mouse mutants. We propose a dual role for Pinch2 in preventing excess of myelin wraps through RhoA-dependent control of membrane growth and in fostering myelin stability via Cdc42-dependent organization of cytoskeletal septins. Together, these findings indicate that IPP-containing Pinch2 is a novel critical cell-autonomous molecular hub ensuring synchronous control of key signaling networks during developmental myelination.Summary statementPinch proteins are core components of a ternary protein complex comprising Ilk and Parvin (IPP). This work identifies Pinch2 as key regulator of the formation and maturation of CNS myelin.

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Section: Discussionsupporting

confidence: 68%

Pinch2 is a novel regulator of myelination in the Central Nervous System

Faria

Vale-Silva

Fässler³

et al. 2022

Preprint

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“…The current notion is that the IPP serves as a signal-processing platform by recruiting a variety of proteins. For example, α -parvin directly interacts with paxillin ( 12 – 14 ), PINCH influences receptor tyrosine kinases ( 15 ), and both parvin and PINCH bind F-actin ( 16 , 17 ), connecting the IPP to the cytoskeleton. Although ILK was believed to directly associate with β -integrin tails ( 18 ), more recent studies show that ILK rather indirectly contacts integrins by binding to kindlin-2 ( 19 , 20 ).…”

mentioning

confidence: 99%

ATP allosterically stabilizes integrin-linked kinase for efficient force generation

Martin

Nava

Wickström

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance The pseudokinase integrin-linked kinase (ILK) is a central component of focal adhesions, cytoplasmic multiprotein complexes that integrate and transduce biochemical and mechanical signals from the extracellular environment into the cell and vice versa. However, the precise molecular functions, particularly the mechanosensory properties of ILK and the significance of retained adenosine triphosphate (ATP) binding, are still unclear. Combining molecular-dynamics simulations with cell biology, we establish a role for ATP binding to pseudokinases. We find that ATP promotes the structural stability of ILK, allosterically influences the interaction between ILK and its binding partner parvin at adhesions, and enhances the mechanoresistance of this complex. On the cellular level, ATP binding facilitates efficient traction force buildup, focal adhesion stabilization, and efficient cell migration.

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“…DMD, a part of the dystrophin-glycoprotein complex, bridges actin and the ECM and is required for the development and organization of myofibers as contractile units in striated muscles [ 38 , 39 , 40 ]. Vinculin is also a cytoskeletal protein associated with the cell–ECM junction [ 41 , 42 ]. Thus, we propose that PXN interacts with the ITGβ6, DMD, and VCL proteins to form a stable scaffold structure to maintain the stability of cell morphology and anchor cells to the basal lamina, thus facilitating the normal physiological functions of satellite cells ( Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

ITGβ6 Facilitates Skeletal Muscle Development by Maintaining the Properties and Cytoskeleton Stability of Satellite Cells

Zhang

Liu

et al. 2022

Life

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Integrin proteins are important receptors connecting the intracellular skeleton of satellite cells and the extracellular matrix (ECM), playing an important role in the process of skeletal muscle development. In this research, the function of ITGβ6 in regulating the differentiation of satellite cells was studied. Transcriptome and proteome analysis indicated that Itgβ6 is a key node connecting ECM-related proteins to the cytoskeleton, and it is necessary for the integrity of the membrane structure and stability of the cytoskeletal system, which are essential for satellite cell adhesion. Functional analysis revealed that the ITGβ6 protein could affect the myogenic differentiation potential of satellite cells by regulating the expression of PAX7 protein, thus regulating the formation of myotubes. Moreover, ITGβ6 is involved in muscle development by regulating cell-adhesion-related proteins, such as β-laminin, and cytoskeletal proteins such as PXN, DMD, and VCL. In conclusion, the effect of ITGβ6 on satellite cell differentiation mainly occurs before the initiation of differentiation, and it regulates terminal differentiation by affecting satellite cell characteristics, cell adhesion, and the stability of the cytoskeleton system.

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Complex structures of Rsu1 and PINCH1 reveal a regulatory mechanism of the ILK/PINCH/Parvin complex for F-actin dynamics

Cited by 13 publications

References 45 publications

Pinch2 is a novel regulator of myelination in the Central Nervous System

Pinch2 is a novel regulator of myelination in the Central Nervous System

ATP allosterically stabilizes integrin-linked kinase for efficient force generation

ITGβ6 Facilitates Skeletal Muscle Development by Maintaining the Properties and Cytoskeleton Stability of Satellite Cells

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