Homing Receptors and Vascular Addressins: Cell Adhesion Molecules that Direct Lymphocyte Traffic

Berg, Ellen L.; Goldstein, Leslie A.; Jimla, Mark A.; Nakache, M.; Picker, Louis J.; Streeter, Philip R.; Wu, Nicholas; Zhou, Daqing; Butcher, Eugene C.

doi:10.1111/j.1600-065x.1989.tb00010.x

Cited by 309 publications

(109 citation statements)

References 39 publications

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“…CD44 is known to have several isoforms due to alternative splicing (Haynes et al, 1991), although not all CD44 variants can bind HA and/or mediate lymphocyte homing (Berg et al, 1989;Stamenkovic et al, 1991). Although layilin genomic clones have not yet been analyzed, it will be of interest to study whether there also exist different layilin isoforms.…”

Section: Discussionmentioning

confidence: 99%

Layilin, a Novel Integral Membrane Protein, Is a Hyaluronan Receptor

Bono

Rubin

Higgins

et al. 2001

MBoC

135

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The actin cytoskeleton plays a significant role in changes of cell shape and motility, and interactions between the actin filaments and the cell membrane are crucial for a variety of cellular processes. Several adaptor proteins, including talin, maintain the cytoskeleton-membrane linkage by binding to integral membrane proteins and to the cytoskeleton. Layilin, a recently characterized transmembrane protein with homology to C-type lectins, is a membrane-binding site for talin in peripheral ruffles of spreading cells. To facilitate studies of layilin's function, we have generated a layilin-Fc fusion protein comprising the extracellular part of layilin joined to human immunoglobulin G heavy chain and used this chimera to identify layilin ligands. Here, we demonstrate that layilin-Fc fusion protein binds to hyaluronan immobilized to Sepharose. Microtiter platebinding assays, coprecipitation experiments, and staining of sections predigested with different glycosaminoglycan-degrading enzymes and cell adhesion assays all revealed that layilin binds specifically to hyaluronan but not to other tested glycosaminoglycans. Layilin's ability to bind hyaluronan, a ubiquitous extracellular matrix component, reveals an interesting parallel between layilin and CD44, because both can bind to cytoskeleton-membrane linker proteins through their cytoplasmic domains and to hyaluronan through their extracellular domains. This parallelism suggests a role for layilin in cell adhesion and motility. INTRODUCTIONCell shape and movement form the basis for several biological phenomena such as morphogenesis, invasion, and metastasis. The actin cytoskeleton is a major determinant of changes in cell shape, and interactions between actin filaments and the cell membrane are essential for cell adhesion, spreading, and migration, as well as for signal transduction (Hall, 1998;Schoenwaelder and Burridge, 1999). Several molecules have been recognized as linkers between the actin cytoskeleton and the cell membrane. For example, members of the band 4.1/ERM superfamily (band 4.1, talin, ezrin, radixin, moesin, and merlin, the product of the neurofibromatosis type 2 tumor suppressor gene) are characterized by the presence of a conserved N-terminal membrane-binding domain, which is able to bind to the cytoplasmic region of several transmembrane receptors, including CD44, CD43, ICAM-2, and ICAM-3 (Sainio et al., 1997;Heiska et al., 1998;Yonemura et al., 1998). The C-terminal regions of ERM proteins are thought to bind to actin filaments, thereby linking these transmembrane receptors to the cytoskeleton (reviewed by Mangeat et al., 1999).Layilin is a recently cloned ϳ55-kDa membrane-binding partner for talin (Borowsky and Hynes, 1998) that is widely expressed in different cell types and tissue extracts. It is found in peripheral ruffles of spreading cells and is recruited to membrane ruffles in cells induced to migrate in in vitro wounding experiments. Layilin colocalizes with talin in ruffles and binds to talin's ϳ50-kDa head domain (amino acids 280 -435)...

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Section: Discussionmentioning

confidence: 99%

Layilin, a Novel Integral Membrane Protein, Is a Hyaluronan Receptor

Bono

Rubin

Higgins

et al. 2001

MBoC

135

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“…At the same time, the cardiovascular system is characterized by a remarkable array of organ-and region-specific endothelial cell properties that collectively give rise to functional specialization of the endothelium (27)(28)(29). For example, the postcapillary high-venuole endothelial cells in lymphoid organs support the binding and migration of lymphocytes via the specific interaction of adhesion molecules with lymphocyte homing receptors (30,31), whereas the endothelial cells that line the small…”

Section: Discussionmentioning

confidence: 99%

A vascular bed–specific pathway regulates cardiac expression of endothelial nitric oxide synthase

Guillot¹,

Guan²,

Liu³

et al. 1999

J. Clin. Invest.

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The endothelial nitric oxide synthase (eNOS) gene is induced by a variety of extracellular signals under both in vitro and in vivo conditions. To gain insight into the mechanisms underlying environmental regulation of eNos expression, transgenic mice were generated with the 1,600-bp 5′ flanking region of the human eNos promoter coupled to the coding region of the LacZ gene. In multiple independent lines of mice, transgene expression was detected within the endothelium of the brain, heart, skeletal muscle, and aorta. β-galactosidase activity was consistently absent in the vascular beds of the liver, kidney, and spleen. In stable transfection assays of murine endothelial progenitor cells, the 1,600-bp promoter region was selectively induced by conditioned media from cardiac myocytes, skeletal myocytes, and brain astrocytes. Cardiac myocyte-mediated induction was partly abrogated by neutralizing anti-plateletderived growth factor (PDGF) antibodies. In addition, promoter activity was upregulated by PDGF-AB. Analysis of promoter deletions revealed that a PDGF response element lies between -744 and -1,600 relative to the start site of transcription, whereas a PDGF-independent cardiac myocyte response element is present within the first 166 bp of the 5′ flanking region. Taken together, these results suggest that the eNos gene is regulated in the cardiac endothelium by both a PDGF-dependent and PDGF-independent microvascular bed-specific signaling pathway. J. Clin. Invest. 103:799-805 (1999).Methods eNOS reporter gene constructs. The various human eNOS promoter constructs were derived from F1 LUC (7). To generate the transgenic construct 1600eNOSlacZ, the KpnI-NotI promoter fragment (-1,600 to +22 bp) was isolated from the F1 LUC vector and inserted into a plasmid-containing LacZ cDNA coupled to the SV40 poly(A) tail (gift from J. Rossant, Mount Sinai Hospital, Toronto, Canada). For stable transfections, the F1 LUC was digested with SmaI, releasing the -744 to -1,600 promoter fragment. The remaining vector was religated, resulting in 744eNOS LUC. The generation of the 166eNOS LUC (also referred to as F6 LUC) has been described previously (7).Generation and analysis of transgenic mice. The 1600eNOSlacZ plasmid was digested with KpnI and NotI to release the Bluescript vector (Stratagene, La Jolla, California, USA), and the fragment consisting of the 1,600-bp eNOS promoter fragment coupled to LacZ was isolated on agarose gel. The DNA was resuspended in injection buffer and injected into fertilized mouse eggs as described previously (16). Transgenic founders were identified by Southern blot analysis using a [ 32 P]dCTP-labeled DNA probe containing LacZ coding sequence. The founders were bred to wild-type FVB mice to generate stable transgenic lines. Tissues were harvested from adult F1 offspring heterozygous for the transgene and processed for LacZ staining as described previously (16). For reverse transcriptase-PCR (RT-PCR), total RNA was harvested from various FVB mouse organs using a guanidinium thiocyanate phenol-chloro...

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“…In the human, 85-95-and 200-kD monomeric glycoproteins of the Hermes/CD44 family have been linked to endothelial binding in peripheral nodes, gut-associated lymphoid tissues (GALT) and rheumatoid synovium (6)(7)(8). In the murine system, an 85-95-kD monomeric glycoprotein (Mell4 antigen or gp9OMeIl4) mediates attachment of normal and malignant lymphoid cells to nodal HEV (5,6). Recently, Holzman et al have identified a 160/1 30-kD heterodimer on murine lymphocytes (Lpam 1) that supports selective binding to the HEV of Peyer's patches and cross-reacts with human VLA4 alpha chain-specific MAbs (9).…”

Section: Introductionmentioning

confidence: 99%

“…Functionally distinct lymphoid adhesion receptors have been described for the HEV of several target organs (4,5). In the human, 85-95-and 200-kD monomeric glycoproteins of the Hermes/CD44 family have been linked to endothelial binding in peripheral nodes, gut-associated lymphoid tissues (GALT) and rheumatoid synovium (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Adhesion molecules of cultured hematopoietic malignancies. A calcium-dependent lectin is the principle mediator of binding to the high endothelial venule of lymph nodes.

Stoolman¹,

Ebling²

1989

J. Clin. Invest.

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This study documents that a calcium-dependent phosphomannosyl-binding site on human lymphoid malignancies mediates attachment to the peripheral node high endothelial venule (PNHEV). The phorbol ester PMA coordinately upregulates lectin activity and binding to the PNHEV in the human T-lymphoblastic cell line Jurkat but not in the less phenotypically mature lines HSB2, Molt4, CEM, and HPB-ALL. In contrast, expression of CD18, CD2, and several common epitopes of the putative adhesion receptor gp90fIerme (CD44) did not correlate with attachment to PNHEV in this series of cell lines. Insensitivity to inhibition by the CD18 MAb TS 1.18, temperature and divalent cation requirements further distinguish the Jurkat-PNHEV adhesive interaction from CD11a/18-and CD2-mediated adhesion. The PMA-induced phenotypic changes in the Jurkat line parallel late thymocyte differentiation as well as lymphocyte activation, suggesting that expression of the endothelial-binding lectin may be linked to one or both of these processes. The lectin-like activity on Jurkat cells is functionally indistinguishable from those previously linked to PNHEV recognition in normal human lymphocytes, normal rat lymphocytes and both normal and malignant murine lymphoid cells. In the mouse, this activity is either contained in or functionally linked to a member of the LEC-CAM family gp9OMeIl4, suggesting that Jurkat cells express the human homologue of the murine nodal homing receptor. Thus cultured T lymphoblastic malignancies express a variety of potential endothelial adhesion molecules but use primarily a highly conserved surface lectin to interact with PNHEV.

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Homing Receptors and Vascular Addressins: Cell Adhesion Molecules that Direct Lymphocyte Traffic

Cited by 309 publications

References 39 publications

Layilin, a Novel Integral Membrane Protein, Is a Hyaluronan Receptor

Layilin, a Novel Integral Membrane Protein, Is a Hyaluronan Receptor

A vascular bed–specific pathway regulates cardiac expression of endothelial nitric oxide synthase

Adhesion molecules of cultured hematopoietic malignancies. A calcium-dependent lectin is the principle mediator of binding to the high endothelial venule of lymph nodes.

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