Topic
INF2
About: INF2 is a research topic. Over the lifetime, 72 publications have been published within this topic receiving 7452 citations. The topic is also known as: C14orf151 & C14orf173.
Papers published on a yearly basis
Papers
TL;DR: Evidence is presented that mutations in the gene encoding α-actinin-4 (ACTN4) are the cause of disease in three families with an autosomal dominant form of FSGS, and Regulation of the actin cytoskeleton of glomerular podocytes may be altered in this group of patients.
Abstract: Focal and segmental glomerulosclerosis (FSGS) is a common, non-specific renal lesion Although it is often secondary to other disorders, including HIV infection, obesity, hypertension and diabetes, FSGS also appears as an isolated, idiopathic condition FSGS is characterized by increased urinary protein excretion and decreasing kidney function Often, renal insufficiency in affected patients progresses to end-stage renal failure, a highly morbid state requiring either dialysis therapy or kidney transplantation Here we present evidence implicating mutations in the gene encoding alpha-actinin-4 (ACTN4; ref 2), an actin-filament crosslinking protein, as the cause of disease in three families with an autosomal dominant form of FSGS In vitro, mutant alpha-actinin-4 binds filamentous actin (F-actin) more strongly than does wild-type alpha-actinin-4 Regulation of the actin cytoskeleton of glomerular podocytes may be altered in this group of patients Our results have implications for understanding the role of the cytoskeleton in the pathophysiology of kidney disease and may lead to a better understanding of the genetic basis of susceptibility to kidney damage
1,228 citations
TL;DR: In this article, a large family with hereditary FSGS carries a missense mutation in the TRPC6 gene on chromosome 11q, encoding the ion-channel protein transient receptor potential cation channel 6 (TRPC6).
Abstract: Focal and segmental glomerulosclerosis (FSGS) is a kidney disorder of unknown etiology, and up to 20% of patients on dialysis have been diagnosed with it. Here we show that a large family with hereditary FSGS carries a missense mutation in the TRPC6 gene on chromosome 11q, encoding the ion-channel protein transient receptor potential cation channel 6 (TRPC6). The proline-to-glutamine substitution at position 112, which occurs in a highly conserved region of the protein, enhances TRPC6-mediated calcium signals in response to agonists such as angiotensin II and appears to alter the intracellular distribution of TRPC6 protein. Previous work has emphasized the importance of cytoskeletal and structural proteins in proteinuric kidney diseases. Our findings suggest an alternative mechanism for the pathogenesis of glomerular disease.
1,087 citations
TL;DR: On the basis of structural and mechanistic work, an integrated model is presented for FH2 processive motion and the signature formin homology 2 (FH2) domain initiates filament assembly and remains persistently associated with the fast-growing barbed end, enabling rapid insertion of actin subunits while protecting the end from capping proteins.
Abstract: Formins are a widely expressed family of proteins that govern cell shape, adhesion, cytokinesis, and morphogenesis by remodeling the actin and microtubule cytoskeletons. These large multidomain proteins associate with a variety of other cellular factors and directly nucleate actin polymerization through a novel mechanism. The signature formin homology 2 (FH2) domain initiates filament assembly and remains persistently associated with the fast-growing barbed end, enabling rapid insertion of actin subunits while protecting the end from capping proteins. On the basis of structural and mechanistic work, an integrated model is presented for FH2 processive motion. The adjacent FH1 domain recruits profilin-actin complexes and accelerates filament elongation. The most predominantly expressed formins in animals and fungi are autoinhibited through intramolecular interactions and appear to be activated by Rho GTPases and additional factors. Other classes of formins lack the autoinhibitory and/or Rho-binding domains and thus are likely to be controlled by alternative mechanisms.
862 citations
TL;DR: It is found that actin polymerization through ER-localized inverted formin 2 (INF2) was required for efficient mitochondrial fission in mammalian cells, and this results provide a potential cellular mechanism for this disease state.
Abstract: Mitochondrial fission is fundamentally important to cellular physiology The dynamin-related protein Drp1 mediates fission, and interaction between mitochondrion and endoplasmic reticulum (ER) enhances fission However, the mechanism for Drp1 recruitment to mitochondria is unclear, although previous results implicate actin involvement Here, we found that actin polymerization through ER-localized inverted formin 2 (INF2) was required for efficient mitochondrial fission in mammalian cells INF2 functioned upstream of Drp1 Actin filaments appeared to accumulate between mitochondria and INF2-enriched ER membranes at constriction sites Thus, INF2-induced actin filaments may drive initial mitochondrial constriction, which allows Drp1-driven secondary constriction Because INF2 mutations can lead to Charcot-Marie-Tooth disease, our results provide a potential cellular mechanism for this disease state
757 citations
TL;DR: The emerging complexity in the mechanisms governing formins mirrors the wide range of essential functions that they perform in cell motility, cell division and cell and tissue morphogenesis.
Abstract: Formins are highly conserved proteins that have essential roles in remodelling the actin and microtubule cytoskeletons to influence eukaryotic cell shape and behaviour. Recent work has identified numerous cellular factors that locally recruit, activate or inactivate formins to bridle and unleash their potent effects on actin nucleation and elongation. The effects of formins on microtubules have also begun to be described, which places formins in a prime position to coordinate actin and microtubule dynamics. The emerging complexity in the mechanisms governing formins mirrors the wide range of essential functions that they perform in cell motility, cell division and cell and tissue morphogenesis.
546 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 2 |
| 2020 | 8 |
| 2019 | 8 |
| 2018 | 7 |
| 2017 | 3 |
| 2016 | 4 |