Cell membranes transmembrane domains

Several nonconventional cadherins that contain cadherin repeats have been described but they have specific features not found in the classical cadherins [1]. The cadherin Flamingo, originally detected in Drosophila, contains seven transmembrane segments and in this respect resembles G protein-coupled receptors. The extracellular domain of Flamingo and its mammalian homologs is composed of cadherin repeats as well as EGF-like and laminin motifs. The seven transmembrane span cadherins have a role in homotypic cell interactions and in the establishment of cell polarity. The FAT-related cadherins are characterized by a large number of cadherin repeats (34 in FAT and 27 in dachsous). Their cytoplasmic domains can bind to catenins. T- (=truncated-)cadherin differs from other cadherins in that it has no transmembrane domain but is attached to the cell membrane via a glycosylpho-sphatidylinositol anchor. 

Cell membrane spanning proteins contain a luminal/ extracellular domain, a transmembrane region and a cytosolic domain. In a type I transmembrane protein the N-terminus is the extracellular/luminal part of the protein, whereas the C-terminus comprises the cytosolic region of the membrane protein. 

The VACM-1 receptor is a membrane-associated protein with a single putative transmembrane domain that binds selectively AVP (XD — 2 nM), but cannot discriminate between VXR and V2R analogues. It is expressed in endothelial and medullary collecting duct cells and upon stimulation by AVP. It induces a mobilization of cytosolic-free Ca2+, decreases cAMP production and inhibits cellular growth via MAPK phosphorylation and p53 expression. The mechanism of action and physiological functions of this new receptor are not well understood, but it seems to participate in the regulation of AVP induced signal transduction pathways or of a yet unidentified peptide. 

Affinity chromatography using factor XII as ligand leads to purification of u-PAR rather selectively, with only trace quantities of cytokeratin 1 or gClqR present [K. Joseph and A. Kaplan, unpubl. observations]. It is of interest that none of these three proteins possesses a transmembrane domain but u-PAR has a phos-phatidylinositol linkage within the cell membrane. Nevertheless, each of them has been isolated from purified cell membranes and they have been demonstrated to exist within the cell membrane by immunoelectron microscopy [41] presumably... 

C-termini and a large glycosylated extracellular loop between transmembrane domains 3 and 4. The proteins show the most homology in their transmembrane spanning domains, particularly domains 1, 2, and 4-8, which may be involved in moving the transmitter across the membrane. The transporters are substrates for PKC-dependent phosphorylation, which reduces their activity. The dopamine transporter is phosphorylated on the extreme end of the N-terminal tail, and consensus phosphorylation sites for various other kinases are present in the intracellular loops and domains [20-22] (Fig. 12-4). The dopamine and norepinephrine transporters form functional homo-oligomers, although it is not known if this is required for transport activity, and the transporters also interact with many other membrane proteins that may control their cell-surface expression or other properties. 

The transmembrane domain in the RPTK is a hydrophobic segment of 22-26 amino acids inserted in the cell membrane. It is flanked by a proline-rich region in the N-terminus and a cluster of basic amino acids in the C-ter-minus. This combination of structures secures the transmembrane domain within the lipid bilayer. There is a low degree of homology in the transmembrane domain, even between two closely related RPTKs, suggesting that the primary sequence contains little information for signal transduction. 

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