scholarly journals Colocalization of IQGAP1 with DLC-1 and PLC-δ1; Its potential role in coronary spasm

2019 ◽  
Author(s):  
Makoto Tanaka ◽  
Tomohiro Osanai ◽  
Yoshimi Homma ◽  
Kenji Hanada ◽  
Ken Okumura ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Calcium Concentration ◽  
Potential Role ◽  
Coronary Spasm ◽  
Lipid Transfer ◽  
Gtpase Activating Protein ◽  
Linear Arrays ◽  
Iq Motif ◽  
Start Domain ◽  
Steroidogenic Acute Regulatory

AbstractPhospholipase C (PLC)-δ1, activated by p122RhoGTPase-activating protein (GAP)/deleted in liver cancer-1 (p122RhoGAP/DLC-1), contributes to the coronary spastic angina (CSA) pathogenesis. The present study aims to further investigate the p122RhoGAP/DLC-1 protein. We examined molecules assisting this protein and identified a scaffold protein—IQ motif-containing GTPase-activating protein 1 (IQGAP1). IQGAP1-C binds to the steroidogenic acute regulatory-related lipid transfer (START) domain of p122RhoGAP/DLC-1, and PLC-δ1 binds to IQGAP1-N, forming a complex. In fluorescence microscopy, small dots of PLC-δ1 created fine linear arrays like microtubules, and IQGAP1 and p122RhoGAP/DLC-1 were colocated in the cytoplasm with PLC-δ1. Ionomycin induced the raft recruitment of the PLC-δ1, IQGAP1, and p122RhoGAP/DLC-1 complex by translocation to the plasma membrane (PM), indicating the movement of this complex is along microtubules with the motor protein kinesin. Moreover, the IQGAP1 protein was elevated in skin fibroblasts obtained from patients with CSA, and it enhanced the PLC activity and peak intracellular calcium concentration in response to acetylcholine. IQGAP1, a novel stimulating protein, forms a complex with p122RhoGAP/DLC-1 and PLC-δ1 that moves along microtubules and enhances the PLC activity.

MLN64 and MENTHO, two mediators of endosomal cholesterol transport

2006 ◽  
Vol 34 (3) ◽  
pp. 343-345 ◽  
Author(s):  
F. Alpy ◽  
C. Tomasetto
Keyword(s):  
Metastatic Lymph Node ◽  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Cholesterol Transport ◽  
Lipid Transfer ◽  
Transmembrane Helices ◽  
Late Endosomes ◽  
Start Domain ◽  
Steroidogenic Acute Regulatory

MLN64 (metastatic lymph node 64) and MENTHO (MLN64 N-terminal homologue) are two late-endosomal proteins that share a conserved region of four transmembrane helices with three short intervening loops called the MENTAL domain (MLN64 N-terminal domain). This domain mediates MLN64 and MENTHO homo- and hetero-interactions, targets both proteins to late endosomes and binds cholesterol in vivo. In addition to the MENTAL domain, MLN64 contains a cholesterol-specific START domain [StAR (steroidogenic acute regulatory protein)-related lipid transfer domain]. The START domain is a protein module of approx. 210 residues that binds lipids, including sterols, and is present in 15 distinct proteins in mammals. Thus MLN64 and MENTHO define discrete cholesterol-containing subdomains within the membrane of late endosomes where they may function in cholesterol transport. The MENTAL domain might serve to maintain cholesterol at the membrane of late endosomes prior to its shuttle to cytoplasmic acceptor(s) through the START domain.

scholarly journals A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Alberto T Gatta ◽  
Louise H Wong ◽  
Yves Y Sere ◽  
Diana M Calderón-Noreña ◽  
Shamshad Cockcroft ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Lipid Transfer ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
New Family ◽  
Sterol Transport ◽  
In Trans ◽  
Membrane Contact ◽  
Start Domain

Sterol traffic between the endoplasmic reticulum (ER) and plasma membrane (PM) is a fundamental cellular process that occurs by a poorly understood non-vesicular mechanism. We identified a novel, evolutionarily diverse family of ER membrane proteins with StART-like lipid transfer domains and studied them in yeast. StART-like domains from Ysp2p and its paralog Lam4p specifically bind sterols, and Ysp2p, Lam4p and their homologs Ysp1p and Sip3p target punctate ER-PM contact sites distinct from those occupied by known ER-PM tethers. The activity of Ysp2p, reflected in amphotericin-sensitivity assays, requires its second StART-like domain to be positioned so that it can reach across ER-PM contacts. Absence of Ysp2p, Ysp1p or Sip3p reduces the rate at which exogenously supplied sterols traffic from the PM to the ER. Our data suggest that these StART-like proteins act in trans to mediate a step in sterol exchange between the PM and ER.

scholarly journals The mammalian START domain protein family in lipid transport in health and disease

2011 ◽  
Vol 212 (3) ◽  
pp. 257-275 ◽  
Author(s):  
Barbara J Clark
Keyword(s):  
Regulatory Protein ◽  
Protein Family ◽  
Lipid Transport ◽  
Lipid Transfer ◽  
Lipid Trafficking ◽  
Disease States ◽  
Health And Disease ◽  
Start Domain ◽  
Domain Protein ◽  
Steroidogenic Acute Regulatory

Lipid transfer proteins of the steroidogenic acute regulatory protein-related lipid transfer (START) domain family are defined by the presence of a conserved ∼210 amino acid sequence that folds into an α/β helix-grip structure forming a hydrophobic pocket for ligand binding. The mammalian START proteins bind diverse ligands, such as cholesterol, oxysterols, phospholipids, sphingolipids, and possibly fatty acids, and have putative roles in non-vesicular lipid transport, thioesterase enzymatic activity, and tumor suppression. However, the biological functions of many members of the START domain protein family are not well established. Recent research has focused on characterizing the cell-type distribution and regulation of the START proteins, examining the specificity and directionality of lipid transport, and identifying disease states associated with dysregulation of START protein expression. This review summarizes the current concepts of the proposed physiological and pathological roles for the mammalian START domain proteins in cholesterol and lipid trafficking.

Proteomics analysis of liver pathological calcification suggests a role for the IQ motif containing GTPase activating protein 1 in myofibroblast function

2009 ◽  
Vol 3 (3) ◽  
pp. 307-321 ◽  
Author(s):  
Fariba Kalantari ◽  
Patrick Auguste ◽  
Tahereh Ziafazeli ◽  
George Tzimas ◽  
Lars Malmström ◽  
...  
Keyword(s):  
Gtpase Activating Protein ◽  
Proteomics Analysis ◽  
Iq Motif ◽  
Pathological Calcification
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