Disease relevance of TSPAN4

• Antibodies to CD9, a tetraspan transmembrane protein, inhibit canine distemper virus-induced cell-cell fusion but not virus-cell fusion [1].
• During studies to identify cellular molecules that could be involved in macrophage infection, we observed inhibition of HIV-1 infection of macrophages by monoclonal antibody (MAb) to the tetraspan transmembrane glycoprotein CD63 [2].
• A tetraspan protein CD9, normally expressed in the myelin sheath of the central and peripheral nervous system, was identified to be up-regulated in mouse brains infected with transmissible spongiform encephalopathy (TSE), by mRNA differential display screening [3].
• In this study we determine by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) the level of 13 tetraspan messages in 21 Burkitt lymphoma (BL) cell lines [4].
• There are no major differences in tetraspan expression pattern among sporadic or endemic tumours, type of translocation or Epstein-Barr virus status, suggesting the original cell of these tumours is the same, probably a late pre-B cell, at the CD9 to CD37 transition point [4].

High impact information on TSPAN4

• Here we show that subsets of MHC class II molecules localize to membrane microdomains together with tetraspan proteins, the peptide editor HLA-DM and the costimulator CD86 [5].
• Antigen-presenting cells deficient in tetraspan microdomains have a reduced capacity to activate CD4+ T cells [5].
• Thus, the organization of uniformly loaded peptide-MHC class II complexes in tetraspan domains may be a very early event that determines both the composition of the immunological synapse and the quality of the subsequent T helper cell response [5].
• The tetraspan molecule CD151, a novel constituent of hemidesmosomes, associates with the integrin alpha6beta4 and may regulate the spatial organization of hemidesmosomes [6].
• CD151 is the only tetraspan identified in hemidesmosomal structures [6].

Biological context of TSPAN4

• When aligned with other TM4SF proteins, the deduced amino acid sequence of NAG-2 showed most identity (34%) to CD53 [7].
• These data suggest the existence of a tetraspan network which, by connecting several molecules, may organize the positioning of cell surface proteins and play a role in signal transduction, cell adhesion, and motility [8].
• During the past few years, significant advances have been made in elucidating the mechanisms by which point mutations and altered gene dosages in tetraspan genes cause neurological disease [9].
• The clone encodes an open reading frame of 253 amino acids that displays 25% to 30% amino acid sequence identity with several members of the newly defined Tetraspan, or Transmembrane 4 superfamily [10].
• Whereas the expression of tetraspan (4-TM) and 7-TM molecules is well documented on mature and immature hematopoietic cells and leukocytes, this 5-TM type of structure containing two large (255-amino acid [aa] and 290-aa) extracellular loops is unique and does not share sequence homology with any known multi-TM family members [11].

Anatomical context of TSPAN4

• Tetraspan antigens and CD98 presented rather unique staining pattern in OA synovium suggesting special roles for each antigen on the synovial lining layer (SLL) [12].
• Flow cytometry, Northern blotting, and immunohistochemistry showed that NAG-2 is widely present in multiple tissues and cell types but is absent from brain, lymphoid cells, and platelets [7].
• Recently, it has been proposed that MHC-II also associates with another type of membrane microdomain, termed tetraspan microdomains [13].
• Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes [14].
• Using affinity chromatography with MAb K41, we purified from HeLa and Vero cell extracts a 26-kDa protein which contained the amino acid sequence TKDEPQRETLK of human CD9, a member of the tetraspan transmembrane or transmembrane 4 superfamily of cell surface proteins [15].

Associations of TSPAN4 with chemical compounds

• A tetraspan membrane glycoprotein produced in the human intestinal epithelium and liver that can regulate cell density-dependent proliferation [16].
• During the process of characterizing one of these novel genes, we have identified a cDNA clone, a homolog of human/mouse transmembrane-4-superfamily (also known as tetraspan) protein, CD151, the expression of which was significantly decreased in rat frontal cortex following chronic (five weeks) lithium treatment [17].
• The crystalline complex of turkey-egg lysozyme (TEL) with di-N-acetylchitobiose (NAG2) was prepared by a soaking method and the structure was determined by X-ray analysis at 1.55 A resolution [18].

Co-localisations of TSPAN4

• Also, two-color immunofluorescence showed that NAG-2 was co-localized with CD81 on the surface of spread HT1080 cells [7].

Regulatory relationships of TSPAN4

• BACKGROUND: Epithelial membrane protein 2 (EMP2) is an estrus-regulated tetraspan protein that is required for endometrial competence in blastocyst implantation [19].

Other interactions of TSPAN4

• To further characterize the tetraspan complexes we have raised and selected monoclonal antibodies (mAb) for their ability to immunoprecipitate a molecule associated with CD9 [20].
• The alpha(3)beta(1)-CD151 association site was then mapped using chimeric alpha(6)/alpha(3) integrins and CD151/NAG2 TM4SF proteins [21].
• T cell-derived microvesicles also contain the tetraspan protein CD63, suggesting that they originate from endocytic compartments [22].
• An mAb raised to highly purified, immunoisolated MIICs from human B lymphoblastoid cells recognized CD82, a member of the tetraspan family of integral membrane proteins [23].
• Gas3/PMP22 is a tetraspan membrane protein highly expressed in myelinating Schwann cells [24].

Analytical, diagnostic and therapeutic context of TSPAN4

• Western blot analysis showed that isolated exosomes were selectively enriched in the tetraspan protein CD63 [25].

References