RHAMM receptor

A vertebrate homologue of the cell cycle control protein CDC37 was recently cloned and found to be an hyaladherin,62 as was a protein that copurified with the splicing factor SF2.63 An intracellular form of the HA receptor RHAMM was demonstrated to regulate erk kinase activity. Changes in function of these intracellular, depending on whether or not they have HA molecules attached, confers another layer of complexity dependent on intracellular hyaluronidase enzymes. 

Mohapatra, S. et al., Soluble hyaluronan receptor RHAMM induces mitotic arrest by suppressing Cdc2 and cyclin B1 expression, J. Exp. Med., 183, 1663, 1996. 

Samuel, S.K. et al., TGF-beta 1 stimulation of cell locomotion utilizes the hyaluronan receptor RHAMM and hyaluronan,./. Cell Biol., 123, 749, 1993. 

Nagy, J. L Hacking, J. Frankenstein, U. N. TurlQ, E. A Requirement of die hyaluronan receptor RHAMM in neurite extension and motility as demonstrated in primary neurons and neuronal cell lines. J. Neurosci. 199. 15,241-252. 

Unlike sulfated polysaccharides, some of the initial proof of HA s ability to interact with living cells came with the observation that hyaluronan accelerates cell growth. It has also been observed that hyaluronan initiates some cell aggregation. This was the first indication of a unique binding of the polysaccharide to the cell surface. Currently, several receptor proteins that bind to the surface of the HA cytoplasmic membrane have been isolated, including high-affinity receptor CD44 and receptor RHAMM (receptor for hyaluronan-mediated motility). 

The other major receptor for HA is receptor for HA-mediated motility (RHAMM),133,134 discovered and characterized by Eva Turley. This receptor is implicated in cell locomotion, focal adhesion turnover, and contact inhibition. It also is expressed in a number of variant isoforms. The interactions between HA and RHAMM regulate locomotion of cells by a complex network of signal transduction events and interaction with the cytoskeleton of cells. It is also an important regulator of cell growth.135... 

The hyaluronasome, because of its ability to respond to extracellular events as well as to the intracellular metabolic state of the cell may contain HA receptors such as RHAMM and CD44, HA synthase enzymes, the hyaluronidases, hyaluronidase inhibitors,247,248 the /i-cxoglycosidascs, and HA-binding proteins such as HABP1.249... 

De novo synthesized HA may be secreted from the cell and subsequently interact with different cell surface receptors, such as CD44, the receptor for HA-mediated motility (RHAMM), the HA receptor for endocytosis (HARE) and many others. It has become evident that these processes mediate at least three different, very important physiological processes signal transduction, formation of pericellular coats, and the receptor-mediated internalization. 

RHAMM is a HA receptor that can be present either on the cell surface, in the cytoplasm or even in the nucleus. Interactions between RHAMM and HA may trigger a lot of cellular signaling pathways, including those that involve protein kinase C, MAP kinases, phosphatidylinositol and tyrosine kinases [125]. Several recent studies have clearly demonstrated the involvement of RHAMM in the locomotion of TGF-)9-stimulated fibroblasts, smooth muscle cells, macrophages as well as Ras-transformed fibroblasts [126], i.e. the processes that are most likely important in the development of cancer. 

Metastasis Hyaluronate receptor CD44 and RHAMM Galectins E Selectins 140] [132]... 

Slevin M, Krupinski J, Gaffney J, Matou S, West D, Delisser H, Savani RC, Kumar S. Hyaluronan-mediated angiogenesis in vascular disease uncovering RHAMM and CD44 receptor signahng pathways. Matrix Biol 2007 26 58-68. 

It has been determined that some cells begin to aggregate after addition of hyaluronan. The observation of aggregation was the first indication that the polysaccharide macromolecule can be bound with the cell surface. At the present time, several protein receptors, which specifically bind biopolymers on the surface of the cytoplasmic membrane, have been isolated. These have a high affinity to the HA receptors CD44 and the receptor for HA-mediated motility (RHAMM) [123]. Another receptor for hyaluronan endocytosis was found on the membrane of the endothelial cells of the liver sinus. It differs significantly from other... 

Hyalhedrins could be divided in three types (1) soluble proteins, (2) proteins that bind hyaluronan with other polymers of extracellular matrix and (3) proteins, which act as cell membrane receptors for hyaluronan. Two receptors, hyalhedrins CD44 and RHAMM, are well known. The main receptor on the cell surface, that is, CD44, has very high afOnity to biopolymers and is expressed by different cell types including fibroblasts, epithelial and some endothelial cells, keratinocytes and others. Figure 2.15 schanatically shows HA s... 

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