Distinct distribution of specific members of protein 4.1 gene family in the mouse nephron.
TL;DR: Distinct distribution of 4.1 proteins along the nephron suggests their involvement in targeting of selected transmembrane proteins in kidney epithelium and, therefore, in regulation of specific kidney functions.
About: This article is published in Kidney International.The article was published on 2003-04-01 and is currently open access. It has received 56 citations till now. The article focuses on the topics: Distal convoluted tubule & Nephron.
Citations
More filters
TL;DR: Genetic associations for susceptibility to diabetic nephropathy are identified at two novel candidate loci near the FRMD3 and CARS genes, which implicates previously unsuspected pathways in the pathogenesis of this important late complication of type 1 diabetes.
Abstract: OBJECTIVE Despite extensive evidence for genetic susceptibility to diabetic nephropathy, the identification of susceptibility genes and their variants has had limited success. To search for genes that contribute to diabetic nephropathy, a genome-wide association scan was implemented on the Genetics of Kidneys in Diabetes collection. RESEARCH DESIGN AND METHODS We genotyped ∼360,000 single nucleotide polymorphisms (SNPs) in 820 case subjects (284 with proteinuria and 536 with end-stage renal disease) and 885 control subjects with type 1 diabetes. Confirmation of implicated SNPs was sought in 1,304 participants of the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study, a long-term, prospective investigation of the development of diabetes-associated complications. RESULTS A total of 13 SNPs located in four genomic loci were associated with diabetic nephropathy with P −5 . The strongest association was at the FRMD3 (4.1 protein ezrin, radixin, moesin [FERM] domain containing 3) locus (odds ratio [OR] = 1.45, P = 5.0 × 10 −7 ). A strong association was also identified at the CARS (cysteinyl-tRNA synthetase) locus (OR = 1.36, P = 3.1 × 10 −6 ). Associations between both loci and time to onset of diabetic nephropathy were supported in the DCCT/EDIC study (hazard ratio [HR] = 1.33, P = 0.02, and HR = 1.32, P = 0.01, respectively). We demonstratedexpression of both FRMD3 and CARS in human kidney. CONCLUSIONS We identified genetic associations for susceptibility to diabetic nephropathy at two novel candidate loci near the FRMD3 and CARS genes. Their identification implicates previously unsuspected pathways in the pathogenesis of this important late complication of type 1 diabetes.
281 citations
Cites background from "Distinct distribution of specific m..."
...1 protein family have well-characterized roles as cytoskeletal proteins, maintaining both cellular shape and form, in a variety of cell types, including mouse nephron (27,28)....
[...]
TL;DR: A functional assay of glomerular filtration barrier revealed that absence of normal nephrin, podocin or mosaic eyes expression results in loss ofglomerularfiltration discrimination and aberrant passage of high molecular weight substances into the glomersular filtrate.
198 citations
Cites background from "Distinct distribution of specific m..."
...1-like genes are expressed in a segment-specific fashion in the mammalian nephron; however, none have so far been shown to be expressed in glomerular podocytes (Ramez et al., 2003)....
[...]
...Several different protein 4.1-like genes are expressed in a segment-specific fashion in the mammalian nephron; however, none have so far been shown to be expressed in glomerular podocytes (Ramez et al., 2003)....
[...]
...1B/EPB41L3 are expressed in distinct nephron cell types (Ramez et al., 2003); however, none have been shown to be expressed in podocytes....
[...]
...In the mouse nephron, protein 4.1 family members 4.1R/EPB4.l, 4.1N/EPB41L1, 4.1G/EPB41L2 and 4.1B/EPB41L3 are expressed in distinct nephron cell types (Ramez et al., 2003); however, none have been shown to be expressed in podocytes....
[...]
TL;DR: It is demonstrated that positive regulation of E16 splicing can be mediated by Fox-2 or Fox-1, two closely related splicing factors that possess identical RNA recognition motifs, and proposed that the Fox family of splicing enhancers plays an important role in alternative splicing switches during differentiation in metazoan organisms.
121 citations
TL;DR: The spectrin–ankyrin–4.1–adducin complex represents a remarkable system that underpins animal life; it has been adapted to many different functions at different times during animal evolution.
Abstract: The cells in animals face unique demands beyond those encountered by their unicellular eukaryotic ancestors. For example, the forces engendered by the movement of animals places stresses on membranes of a different nature than those confronting free-living cells. The integration of cells into tissues, as well as the integration of tissue function into whole animal physiology, requires specialisation of membrane domains and the formation of signalling complexes. With the evolution of mammals, the specialisation of cell types has been taken to an extreme with the advent of the non-nucleated mammalian red blood cell. These and other adaptations to animal life seem to require four proteins—spectrin, ankyrin, 4.1 and adducin—which emerged during eumetazoan evolution. Spectrin, an actin cross-linking protein, was probably the earliest of these, with ankyrin, adducin and 4.1 only appearing as tissues evolved. The interaction of spectrin with ankyrin is probably a prerequisite for the formation of tissues; only with the advent of vertebrates did 4.1 acquires the ability to bind spectrin and actin. The latter activity seems to allow the spectrin complex to regulate the cell surface accumulation of a wide variety of proteins. Functionally, the spectrin–ankyrin–4.1–adducin complex is implicated in the formation of apical and basolateral domains, in aspects of membrane trafficking, in assembly of certain signalling and cell adhesion complexes and in providing stability to otherwise mechanically fragile cell membranes. Defects in this complex are manifest in a variety of hereditary diseases, including deafness, cardiac arrhythmia, spinocerebellar ataxia, as well as hereditary haemolytic anaemias. Some of these proteins also function as tumor suppressors. The spectrin–ankyrin–4.1–adducin complex represents a remarkable system that underpins animal life; it has been adapted to many different functions at different times during animal evolution.
116 citations
Cites background from "Distinct distribution of specific m..."
...In the kidney (Ramez et al. 2003; Gascard et al. 2004) and heart (Taylor-Harris et al....
[...]
...In the kidney (Ramez et al. 2003; Gascard et al. 2004) and heart (Taylor-Harris et al. 2005b), all the 4.1 proteins are subject to splice regulation, and this now appears to be common to most, if not all, tissues (Parra et al. 2004)....
[...]
TL;DR: It is hypothesized that differential regulation of 4.1 proteins and ankyrins allows highly selective control of cell surface protein accumulation and, hence, function.
114 citations
References
More filters
TL;DR: This review deals with the molecular physiology of spectrin, ankyrin, which links spectrin to the anion exchanger, and two spectrin-associated proteins that promote spectrin interactions with actin: adducin and protein 4.1.
Abstract: The spectrin-based membrane skeleton of the humble mammalian erythrocyte has provided biologists with a set of interacting proteins with diverse roles in organization and survival of cells in metazoan organisms. This review deals with the molecular physiology of spectrin, ankyrin, which links spectrin to the anion exchanger, and two spectrin-associated proteins that promote spectrin interactions with actin: adducin and protein 4.1. The lack of essential functions for these proteins in generic cells grown in culture and the absence of their genes in the yeast genome have, until recently, limited advances in understanding their roles outside of erythrocytes. However, completion of the genomes of simple metazoans and application of homologous recombination in mice now are providing the first glimpses of the full scope of physiological roles for spectrin, ankyrin, and their associated proteins. These functions now include targeting of ion channels and cell adhesion molecules to specialized compartments within the plasma membrane and endoplasmic reticulum of striated muscle and the nervous system, mechanical stabilization at the tissue level based on transcellular protein assemblies, participation in epithelial morphogenesis, and orientation of mitotic spindles in asymmetric cell divisions. These studies, in addition to stretching the erythrocyte paradigm beyond recognition, also are revealing novel cellular pathways essential for metazoan life. Examples are ankyrin-dependent targeting of proteins to excitable membrane domains in the plasma membrane and the Ca(2+) homeostasis compartment of the endoplasmic reticulum. Exciting questions for the future relate to the molecular basis for these pathways and their roles in a clinical context, either as the basis for disease or more positively as therapeutic targets.
942 citations
TL;DR: Evidence for possible movement of ions and carbon dioxide through the aquaporins is reviewed here, as well as evidence for direct regulation of aquaporin function by posttranslational modification such as phosphorylation.
Abstract: The aquaporins (AQPs) are a family of small membrane-spanning proteins (monomer size ∼30 kDa) that are expressed at plasma membranes in many cells types involved in fluid transport. This review is ...
645 citations
TL;DR: How molecular events at the transporter level account for the physiological changes in tubular handling of sodium promoted by hormones is analyzed to analyze the integrated network of signaling pathways underlying hormone action.
Abstract: Tubular reabsorption of filtered sodium is quantitatively the main contribution of kidneys to salt and water homeostasis The transcellular reabsorption of sodium proceeds by a two-step mechanism:
470 citations
"Distinct distribution of specific m..." refers background in this paper
...At the cellular level, a large part of this molecular traffic occurs through specific transporters whose activity is mostly controlled by various hormones and neuromediator...
[...]
TL;DR: It is shown that the plasma membrane ion exchanger NHE1 acts as an anchor for actin filaments to control the integrity of the cortical cytoskeleton through a previously unrecognized structural link between N HE1 and the actin binding proteins ezrin, radixin, and moesin.
407 citations
"Distinct distribution of specific m..." refers background in this paper
...The functional impact of such interactions has been further emphasized by the observation that NHEs are involved in organization of cortical cytoskeleton and in control of cell shape independently of ion transport activit...
[...]
TL;DR: The ERM family consists of three closely related proteins, ezrin, radixin, and moesin, that are thought to work as cross-linkers between plasma membranes and actin-based cytoskeletons.
363 citations