The bulletin of the Yamaguchi Medical School

Continued by:Medical Science & Innovation
EISSN:2758-5441

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The bulletin of the Yamaguchi Medical School Volume 55 Issue 3-4
published_at 2008

Role of alpha-actinin-4 in the regulation of endocytosis

Role of alpha-actinin-4 in the regulation of endocytosis
Hara Tomohiko
Honda Kazufumi
Shitashige Miki
Ono Masaya
Naito Katsusuke
Hirohashi Setsuo
Yamada Tesshi
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A050055000301.pdf
Descriptions
Alpha-actinin-4, originally identified as an actin-binding protein, has been associated with cell motility and cancer invasion. However, it forms complexes with a diverse array of partner proteins and is speculated to exert several distinct functions based on the characteristics of these proteins. Immunoprecipitation and mass spectrometric analysis reveal that alpha-actinin-4 forms native complexes with several partner proteins in 22RV1 cells, including β/γ-actin, clathrin heavy chain and nonmuscular myosin heavy chain. Clathrin is a coat protein that covers the internalized membrane pit and plays a central role in early endocytosis. We identified other clathrin-related and unrelated cargo proteins, including dynamin, adaptin-γ, β-NAP and p47A, that interact with alpha-actinin-4. Immunofluorescence microscopy revealed that dynamin and clathrin are co-localized with alpha-actinin-4 at the dorsal sites of membrane rufflings, and the transfection of ACTN4 cDNA facilitates the transport of transferrin into the peri-nuclear endosomes. In this review, we report that alpha-actinin-4 is involved in the regulation of endocytosis. Endocytosis enforces termination of signalling evoked by the cell surface receptors and regulates recycling of receptors and ligands. The change of alpha-actinin-4 expression levels may therefore induce aberrations in the intracellular trafficking of various cell surface molecules, such as growth factors and receptors.
Creator Keywords
actinin-4
endocytosis
clathrin
proteomics