Syndecans-2 and -4; Close Cousins, but not IdenticalTwins

John R. Couchman,Eok-Soo Oh 한국분자세포생물학회 2004 Molecules and cells Vol.17 No.2

The vertebrate syndecans, which make up a four-member family of small type I transmembrane heparan sulfate proteoglycans, constitute evolutionarily con-served family proteins. In particular, sequences in the transmembrane and cytoplasmic domains are a unify-ing feature within the family. However, the extracellular domain sequences are molecule-specific, implying that different syndecans have evolved to carry out similar, but non-identical, functions. While all four syndecans have been implicated in regulation of the cytoskeleton, their roles are clearly complex. Recent developments indicate that the closely related syndecan-2 and -4 have separable functions, though both bind a number of ligands through their heparan sulfate chains. The speci-fication of these activities is probably core protein re-lated, but is it due to a distinct expression pattern or molecule-specific regulatory mechanisms? Although there is not yet enough data to provide unambiguous answers, here we shall review the known functions and regulatory mechanisms of syndecan-2 and -4.

Syndecans-2 and -4; close cousins, but not identical twins.

Oh, Eok-Soo,Couchman, John R Korean Society for Molecular Biology 2004 Molecules and cells Vol.17 No.2

<P>The vertebrate syndecans, which make up a four-member family of small type I transmembrane heparan sulfate proteoglycans, constitute evolutionarily conserved family proteins. In particular, sequences in the transmembrane and cytoplasmic domains are a unifying feature within the family. However, the extracellular domain sequences are molecule-specific, implying that different syndecans have evolved to carry out similar, but non-identical, functions. While all four syndecans have been implicated in regulation of the cytoskeleton, their roles are clearly complex. Recent developments indicate that the closely related syndecan-2 and -4 have separable functions, though both bind a number of ligands through their heparan sulfate chains. The specification of these activities is probably core protein related, but is it due to a distinct expression pattern or molecule-specific regulatory mechanisms? Although there is not yet enough data to provide unambiguous answers, here we shall review the known functions and regulatory mechanisms of syndecan-2 and -4.</P>

Structural and Cell Adhesion Properties of Zebrafish Syndecan-4 Are Shared with Higher Vertebrates

Whiteford, J.R.,Ko, S.,Lee, W.,Couchman, J.R. The American Society for Biochemistry and Molecula 2008 The Journal of biological chemistry Vol.283 No.43

Haloes at the ragged edge: the importance of the splashback radius

Snaith, O. N.,Bailin, J.,Knebe, A.,Stinson, G.,Wadsley, J.,Couchman, H. Oxford University Press 2017 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.472 No.3

<P>We have explored the outskirts of dark matter haloes out to 2.5 times the virial radius using a large sample of haloes drawn from Illustris, along with a set of zoom simulations (MUGS). Using these, we make a systematic exploration of the shape profile beyond Rvir. In the mean sphericity profile of Illustris haloes, we identify a dip close to the virial radius, which is robust across a broad range of masses and infall rates. The inner edge of this feature may be related to the virial radius and the outer edge with the splashback radius. Due to the high halo-to-halo variation, this result is visible only on average. However, in four individual haloes in the MUGS sample, a decrease in the sphericity and a subsequent recovery is evident close to the splashback radius. We find that this feature persists for several Gyr, growing with the halo. This feature appears at the interface between the spherical halo density distribution and the filamentary structure in the environment. The shape feature is strongest when there is a high rate of infall, implying that the effect is due to the mixing of accreting and virializing material. The filamentary velocity field becomes rapidlymixed in the halo region inside the virial radius, with the area between this and the splashback radius serving as the transition region. We also identify a long-lasting and smoothly evolving splashback region in the radial density gradient in many of the MUGS haloes.</P>

Keratinocytes negatively regulate the N-cadherin levels of melanoma cells via contact-mediated calcium regulation

Chung, Heesung,Jung, Hyejung,Jho, Eek-hoon,Multhaupt, Hinke A.B.,Couchman, John R.,Oh, Eok-Soo Elsevier 2018 Biochemical and biophysical research communication Vol.503 No.2

<P><B>Abstract</B></P> <P>In human skin, melanocytes and their neighboring keratinocytes have a close functional interrelationship. Keratinocytes, which represent the prevalent cell type of human skin, regulate melanocytes through various mechanisms. Here, we use a keratinocyte and melanoma co-culture system to show for the first time that keratinocytes regulate the cell surface expression of N-cadherin through cell-cell contact. Compared to mono-cultured human melanoma A375 cells, which expressed high levels of N-cadherin, those co-cultured with the HaCaT human keratinocyte cell line showed reduced levels of N-cadherin. This reduction was most evident in areas of A375 cells that underwent cell-cell contact with the HaCaT cells, whereas HaCaT cell-derived extracellular matrix and conditioned medium both failed to reduce N-cadherin levels. The intracellular level of calcium in co-cultured A375 cells was lower than that in mono-cultured A375 cells, and treatment with a cell-permeant calcium chelator (BAPTA) reduced the N-cadherin level of mono-cultured A375 cells. Furthermore, co-culture with HaCaT cells reduced the expression levels of transient receptor potential cation channel (TRPC) 1, −3 and −6 in A375 cells, and siRNA-mediated multi-depletion of TRPC1, -3 and -6 reduced the N-cadherin level in these cells. Taken together, these data suggest that keratinocytes negatively regulate the N-cadherin levels of melanoma cells via cell-to-cell contact-mediated calcium regulation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Human keratinocyte cells reduce the N-cadherin levels of co-cultured melanoma cells. </LI> <LI> Cell-to-cell contact is necessary for this keratinocyte-mediated N-cadherin reduction. </LI> <LI> Keratinocytes reduce intracellular calcium in co-cultured melanoma cells. </LI> <LI> Keratinocytes reduce the expression of TRPCs in contacting melanoma cells. </LI> </UL> </P>

Serine 34 Phosphorylation of Rho Guanine Dissociation Inhibitor (RhoGDIα) Links Signaling from Conventional Protein Kinase C to RhoGTPase in Cell Adhesion

Dovas, Athanassios,Choi, Youngsil,Yoneda, Atsuko,Multhaupt, Hinke A. B.,Kwon, Seung-Hae,Kang, Dongmin,Oh, Eok-Soo,Couchman, John R. American Society for Biochemistry and Molecular Bi 2010 The Journal of biological chemistry Vol.285 No.30

<P>Conventional protein kinase C (PKC) isoforms are essential serine/threonine kinases regulating many signaling networks. At cell adhesion sites, PKCα can impact the actin cytoskeleton through its influence on RhoGTPases, but the intermediate steps are not well known. One important regulator of RhoGTPase function is the multifunctional guanine nucleotide dissociation inhibitor RhoGDIα that sequesters several related RhoGTPases in an inactive form, but it may also target them through interactions with actin-associated proteins. Here, it is demonstrated that conventional PKC phosphorylates RhoGDIα on serine 34, resulting in a specific decrease in affinity for RhoA but not Rac1 or Cdc42. The mechanism of RhoGDIα phosphorylation is distinct, requiring the kinase and phosphatidylinositol 4,5-bisphosphate, consistent with recent evidence that the inositide can activate, localize, and orient PKCα in membranes. Phosphospecific antibodies reveal endogenous phosphorylation in several cell types that is sensitive to adhesion events triggered, for example, by hepatocyte growth factor. Phosphorylation is also sensitive to PKC inhibition. Together with fluorescence resonance energy transfer microscopy sensing GTP-RhoA levels, the data reveal a common pathway in cell adhesion linking two essential mediators, conventional PKC and RhoA.</P>