Formin proteins catalyze actin nucleation and microfilament polymerization. Inverted formin 2 (INF2) is an atypical diaphanous-related formin characterized by polymerization and depolymerization of actin. Accumulating evidence showed that INF2 is associated with kidney disease focal segmental glomerulosclerosis and cancers, such as colorectal and thyroid cancer where it functions as a tumor suppressor, glioblastoma, breast, prostate, and gastric cancer, via its oncogenic function. However, studies on the underlying molecular mechanisms of the different roles of INF2 in diverse cancers are limited. This review comprehensively describes the structure, biochemical features, and primary pathogenic mutations of INF2.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1007/s11033-021-06869-x | DOI Listing |
Nat Commun
January 2025
Groupe de Recherche en Signalisation Cellulaire and Département de Biologie Médicale, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada.
Mitochondria are crucial for cellular metabolism and signalling. Mitochondrial activity is modulated by mitochondrial fission and fusion, which are required to properly balance metabolic functions, transfer material between mitochondria, and remove defective mitochondria. Mitochondrial fission occurs at mitochondria-endoplasmic reticulum (ER) contact sites, and requires the formation of actin filaments that drive mitochondrial constriction and the recruitment of the fission protein DRP1.
View Article and Find Full Text PDFKidney360
December 2024
Division of Nephrology, Stead Family Department of Pediatrics, Carver College of Medicine, the University of Iowa.
Background: The p.Arg218Gln (R218Q) mutation in the inverted formin 2 (INF2) gene causes podocytopathy prone to focal segmental glomerulosclerosis (FSGS). This mutation disrupts the ability of INF2 to sequester DYNLL1, thus promoting dynein-mediated mistrafficking of the slit diaphragm protein, nephrin, to proteolytic pathways.
View Article and Find Full Text PDFBMC Nephrol
November 2024
Department of Nephrology (Key Laboratory of Management of Kidney Disease in Zhejiang Province), Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Tiyuchang Road 453, Hangzhou, 310007, People's Republic of China.
Background: Renal disease is associated with Charcot-Marie-Tooth disease (CMT), a common inherited neurological disorder. Three forms of CMT have been identified: CMT1 of the demyelinating type, CMT2 of the axonal defect type, and intermediate type (Int-CMT). INF2 is an important target for variants that cause the complex symptoms of focal segmental glomerulosclerosis (FSGS) and CMT.
View Article and Find Full Text PDFCell Mol Life Sci
November 2024
Centro de Biología Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), 28049, Madrid, Spain.
Formins are proteins that catalyze the formation of linear filaments made of actin. INF2, a formin, is crucial for correct vesicular transport, microtubule stability and mitochondrial division. Its activity is regulated by a complex of cyclase-associated protein and lysine-acetylated G-actin (KAc-actin), which helps INF2 adopt an inactive conformation through the association of its N-terminal diaphanous inhibitory domain (DID) with its C-terminal diaphanous autoinhibitory domain.
View Article and Find Full Text PDFSci Adv
November 2024
Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Heterozygosity for inverted formin-2 (INF2) mutations causes focal segmental glomerulosclerosis (FSGS) with or without Charcot-Marie-Tooth disease. A key question is whether the disease is caused by gain-of-function effects on INF2 or loss of function (haploinsufficiency). Despite established roles in multiple cellular processes, neither INF2 knockout mice nor mice with a disease-associated point mutation display an evident kidney or neurologic phenotype.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!