Role of Swiprosin-1/EFHD2 as a biomarker in the development of chronic diseases

Puttalingaiah, Ramesh Thylur

doi:10.1016/j.lfs.2022.120462

Cited by 2 publications

(3 citation statements)

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Section: Introductionmentioning

confidence: 99%

“…EF-hand domain-containing protein D2 (also known as Swiprosin-1) is a calcium-binding protein with two conserved EF-chiral coiled-coil structural domains, and it is mostly involved in calcium signaling, cytoskeleton assembly and synapse formation 12 – 14 . EFHD2 is broadly expressed in various cell types, with particularly high expression in neurons 12 . The studies of the pathological role of EFHD2 therefore have focused on behavioral pathologies, neurological disorders, and neurodegenerative diseases 12 , 15 – 17 , highlighting the role of EFHD2 in regulating the membrane-cytoplasm trafficking of membrane-associated proteins.…”

Section: Introductionmentioning

confidence: 99%

“…EFHD2 is broadly expressed in various cell types, with particularly high expression in neurons 12 . The studies of the pathological role of EFHD2 therefore have focused on behavioral pathologies, neurological disorders, and neurodegenerative diseases 12 , 15 – 17 , highlighting the role of EFHD2 in regulating the membrane-cytoplasm trafficking of membrane-associated proteins. Our previous study showed that EFHD2 can interact with phosphorylated IFN-γR2 to promote IFN-γR2 trafficking from Golgi to cell membrane of macrophages upon intracellular bacterial infection, which facilitates subsequent IFN-γ signaling in innate response 18 .…”

Section: Introductionmentioning

confidence: 99%

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EFHD2 suppresses intestinal inflammation by blocking intestinal epithelial cell TNFR1 internalization and cell death

Wu,

Xu,

Duan

et al. 2024

Nat Commun

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TNF acts as one pathogenic driver for inducing intestinal epithelial cell (IEC) death and substantial intestinal inflammation. How the IEC death is regulated to physiologically prevent intestinal inflammation needs further investigation. Here, we report that EF-hand domain-containing protein D2 (EFHD2), highly expressed in normal intestine tissues but decreased in intestinal biopsy samples of ulcerative colitis patients, protects intestinal epithelium from TNF-induced IEC apoptosis. EFHD2 inhibits TNF-induced apoptosis in primary IECs and intestinal organoids (enteroids). Mice deficient of Efhd2 in IECs exhibit excessive IEC death and exacerbated experimental colitis. Mechanistically, EFHD2 interacts with Cofilin and suppresses Cofilin phosphorylation, thus blocking TNF receptor I (TNFR1) internalization to inhibit IEC apoptosis and consequently protecting intestine from inflammation. Our findings deepen the understanding of EFHD2 as the key regulator of membrane receptor trafficking, providing insight into death receptor signals and autoinflammatory diseases.

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Section: Introductionmentioning

confidence: 99%