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Age-Onset Phosphorylation of a Minor Actin Variant Promotes Intestinal Barrier Dysfunction.

07:00 EST 2nd December 2019 | BioPortfolio

Summary of "Age-Onset Phosphorylation of a Minor Actin Variant Promotes Intestinal Barrier Dysfunction."

Age-associated decay of intercellular interactions impairs the cells' capacity to tightly associate within tissues and form a functional barrier. This barrier dysfunction compromises organ physiology and contributes to systemic failure. The actin cytoskeleton represents a key determinant in maintaining tissue architecture. Yet, it is unclear how age disrupts the actin cytoskeleton and how this, in turn, promotes mortality. Here, we show that an uncharacterized phosphorylation of a low-abundant actin variant, ACT-5, compromises integrity of the C. elegans intestinal barrier and accelerates pathogenesis. Age-related loss of the heat-shock transcription factor, HSF-1, disrupts the JUN kinase and protein phosphatase I equilibrium which increases ACT-5 phosphorylation within its troponin binding site. Phosphorylated ACT-5 accelerates decay of the intestinal subapical terminal web and impairs its interactions with cell junctions. This compromises barrier integrity, promotes pathogenesis, and drives mortality. Thus, we provide the molecular mechanism by which age-associated loss of specialized actin networks impacts tissue integrity.

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This article was published in the following journal.

Name: Developmental cell
ISSN: 1878-1551
Pages: 587-601.e7

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Medical and Biotech [MESH] Definitions

A membrane and ACTIN CYTOSKELETON associated, N-terminal myristoylated protein that binds CALMODULIN and is a prominent substrate for PROTEIN KINASE C. Both phosphorylation and poly(ADP)-ribosylation inhibit its F-ACTIN crosslinking activity; phosphorylation also causes MARCKS to relocate from the membrane to cytoplasm.

A microfilament protein that interacts with F-ACTIN and regulates cortical actin assembly and organization. It is also an SH3 DOMAIN containing phosphoprotein, and it mediates tyrosine PHOSPHORYLATION based SIGNAL TRANSDUCTION by PROTO-ONCOGENE PROTEIN PP60(C-SRC).

One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments.

A family of low MOLECULAR WEIGHT actin-binding proteins found throughout eukaryotes. They remodel the actin CYTOSKELETON by severing ACTIN FILAMENTS and increasing the rate of monomer dissociation.

An actin capping protein that binds to the barbed-ends of ACTIN filaments. It is a heterodimer consisting of an alpha and a beta subunit. It regulates actin assembly by stabilizing actin oligomers for elongation. In SKELETAL MUSCLE, CapZ is localized to the Z-disk.

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