Protein 4.1G binds to a unique motif within the Fc-gamma RI cytoplasmic tail

The C-terminal domain of protein 4.1G was identified to interact with the cytosolic tail of the high affinity IgG receptor, Fc gamma RI, in yeast two-hybrid screens. Proteins of the 4.1 family have previously been found to mediate receptor/cytoskeleton interactions. In the study presented here, we show an alternatively spliced 4.1G product to be associated with increased Fc-gamma RI binding in yeast two-hybrid assays, and to be selectively enriched in most immune cells at the transcript level. In addition, a detailed analysis of the 4.1G 'docking site' within Fc gamma RI is provided by examining Fc gamma RI-CY-truncated and alanine-substituted mutants. These pointed to an Fc gamma RI membrane-proximal core motif of HxxBxxxBB (H represents hydrophobic residues, B basic residues and x represents any residue), followed by hydrophobic and (potentially) negatively charged residues to be central for interaction with protein 4.1G. (C) 2007 Elsevier Ltd. All rights reserved

Filamin A stabilizes Fc gamma RI surface expression and prevents its lysosomal routing

Filamin A, or actin-binding protein 280, is a ubiquitously expressed cytosolic protein that interacts with intracellular domains of multiple receptors to control their subcellular distribution, and signaling capacity. In this study, we document interaction between Fc gamma RI, a high-affinity IgG receptor, and filamin A by yeast two-hybrid techniques and coimmunoprecipitation. Both proteins colocalized at the plasma membrane in monocytes, but dissociated upon Fc gamma RI triggering. The filamin-deficient cell line M2 and a filamin-reconstituted M2 subclone (A7), were used to further study Fc gamma RI-filamin interactions. Fc gamma RI transfection in A7 cells with filamin resulted in high plasma membrane expression levels. In filamin-deficient M2 cells and in filamin RNA-interference studies, Fc gamma RI surface expression was consistently reduced. Fc gamma RI localized to LAMP-1-positive vesicles in the absence of filamin as shown by confocal microscopy indicative for lysosomal localization. Mouse IgG2a capture experiments suggested a transient membrane expression of Fc gamma RI before being transported to the lysosomes. These data support a pivotal role for filamin in Fc gamma RI surface expression via retention of Fc gamma RI from a default lysosomal pathway

Determinants of suboptimal blood pressure control in a multi‐ethnic population: The Healthy Life in an Urban Setting (HELIUS) study

Among ethnic minority groups in Europe, blood pressure (BP) control is often suboptimal. We aimed to identify determinants of suboptimal BP control in a multi‐ethnic population. We analyzed cross‐sectional data of the Healthy Life in an Urban Setting (HELIUS) study, including 3571 participants aged 18‐70 with prescribed antihypertensive medication, of various ethnic backgrounds (500 Dutch, 1052 African Surinamese, 656 South‐Asian Surinamese, 637 Ghanaian, 433 Turkish, and 293 Moroccan) living in Amsterdam, the Netherlands. 53.3% of the population had suboptimal BP control, defined as BP ≥140/90 mmHg despite prescribed antihypertensives. Using multivariate logistic regression analysis, female sex (OR 0.50, 95%CI 0.43‐0.59), being married (0.83, 0.72‐0.96), smoking (0.78, 0.65‐0.94), alcohol intake (0.80, 0.66‐0.96), obesity (1.67, 1.35‐2.06), cardiovascular disease (CVD) history (0.56, 0.46‐0.68), non‐adherence to antihypertensives (1.26, 1.00‐1.58), and family history of hypertension (1.19, 1.02‐1.38) were identified to be independently associated with suboptimal BP control in the total population. In the ethnic‐stratified analysis, factors associated with better BP control were female sex (all ethnic groups), smoking (Turks), and CVD history (Dutch, South‐Asian Surinamese, and African Surinamese), whereas factors associated with suboptimal BP control were older age (Turks), obesity (Dutch, African Surinamese, Ghanaian, and Turks), and non‐adherence to antihypertensives (Dutch). In conclusion, our analysis identifies several key determinants that are independently associated with suboptimal BP control in a multi‐ethnic population, with some important variations between ethnic groups. Targeting these determinants may help to improve BP control

Determinants of suboptimal blood pressure control in a multi-ethnic population: The Healthy Life in an Urban Setting (HELIUS) study

Among ethnic minority groups in Europe, blood pressure (BP) control is often suboptimal. We aimed to identify determinants of suboptimal BP control in a multi-ethnic population. We analyzed cross-sectional data of the Healthy Life in an Urban Setting (HELIUS) study, including 3571 participants aged 18-70 with prescribed antihypertensive medication, of various ethnic backgrounds (500 Dutch, 1052 African Surinamese, 656 South-Asian Surinamese, 637 Ghanaian, 433 Turkish, and 293 Moroccan) living in Amsterdam, the Netherlands. 53.3% of the population had suboptimal BP control, defined as BP ≥140/90 mmHg despite prescribed antihypertensives. Using multivariate logistic regression analysis, female sex (OR 0.50, 95%CI 0.43-0.59), being married (0.83, 0.72-0.96), smoking (0.78, 0.65-0.94), alcohol intake (0.80, 0.66-0.96), obesity (1.67, 1.35-2.06), cardiovascular disease (CVD) history (0.56, 0.46-0.68), non-adherence to antihypertensives (1.26, 1.00-1.58), and family history of hypertension (1.19, 1.02-1.38) were identified to be independently associated with suboptimal BP control in the total population. In the ethnic-stratified analysis, factors associated with better BP control were female sex (all ethnic groups), smoking (Turks), and CVD history (Dutch, South-Asian Surinamese, and African Surinamese), whereas factors associated with suboptimal BP control were older age (Turks), obesity (Dutch, African Surinamese, Ghanaian, and Turks), and non-adherence to antihypertensives (Dutch). In conclusion, our analysis identifies several key determinants that are independently associated with suboptimal BP control in a multi-ethnic population, with some important variations between ethnic groups. Targeting these determinants may help to improve BP control