Alternative titles; symbols
HGNC Approved Gene Symbol: ICAM5
Cytogenetic location: 19p13.2 Genomic coordinates (GRCh38): 19:10,289,952-10,296,778 (from NCBI)
Yoshihara and Mori (1994) reviewed information on a brain segment-specific cell adhesion molecule, telencephalin. Neuronal surface membranes are polarized into axonal membrane and soma-dendritic membrane. Telencephalin was the first described example of a dendritic cell adhesion molecule. A large number of axonal cell adhesion molecules have been identified and categorized into 3 different groups: the Ig superfamily, the cadherin superfamily (see 192090), and the integrin family (see 135630). Telencephalin was discovered through production of a library of monoclonal antibodies (mAbs) against the dendrodendritic synaptosomal fraction of the rabbit olfactory bulb. By immunohistochemical studies, 1 mAb selectively labeled gray matter of all regions in the telencephalon but no brain segments more caudal to the telencephalon. The 130-kD membrane glycoprotein recognized by this mAb was thus designated telencephalin. Yoshihara et al. (1994) cloned the rabbit TLCN cDNA and demonstrated that rabbit TLCN is a type 1 integral membrane protein with a 29-amino acid signal peptide, a 792-amino acid extracellular region, a 30-amino acid transmembrane region, and a 61-amino acid cytoplasmic region. The extracellular portion of TLCN contains 9 tandem repeats of C2-type immunoglobulin-like domains with intrachain disulfide bonds. Several of these domains of mouse TLCN share high amino acid identity with the corresponding domains of ICAM3 (146631). Yoshihara and Mori (1994) suggested that telencephalin is involved in signaling specific subsets of growing axons to make proper synaptic connections.
Mizuno et al. (1997) isolated cDNA encoding human telencephalin. The 924-amino acid polypeptide comprises an N-terminal signal peptide, an extracellular region with 9 Ig-like domains, a single transmembrane region, and a C-terminal cytoplasmic tail.
Mizuno et al. (1997) showed that recombinant telencephalin interacted with lymphocyte function-associated antigen-1 (LFA1; see 153370/600065) in a divalent cation-independent, phorbol myristate acetate (PMA)-independent manner, which was unusual for interactions mediated by integrins such as LFA1.
Rieckmann et al. (1998) suggested that because of its expression exclusively in neurons, telencephalin might have diagnostic usefulness. The measurements of soluble telencephalin in the serum and cerebrospinal fluid of patients with neurologic diseases by an immunoassay indicated that soluble telencephalin is a neuron-specific molecule that signals ongoing pathophysiologic events in the mesiotemporal or hippocampal areas, reflecting degeneration of telencephalin-expressing neurons or locally compromised blood-brain-barrier function. Since increased serum concentrations were detectable only in patients with temporal lobe epilepsy but not in healthy donors and patients with generalized epilepsy, telencephalin may be useful in the differential diagnosis of seizures.
By yeast 2-hybrid analysis and protein-protein pull-down assays, Annaert et al. (2001) found that mouse Tln interacted with 8 C-terminal amino acids and the first N-terminal transmembrane domain of presenilin-1 (PS1; 104311). In cultured mouse primary hippocampal neurons, Tln localized to the somatodendritic plasma membrane and to the endoplasmic reticulum (ER). Tln colocalized with Ps1 only in the ER. Primary hippocampal neurons derived from Ps1 -/- mouse embryos showed a higher Tln concentration than wildtype neurons, and Tln immunoreactivity accumulated in large honeycomb-like structures near the cell surface. This accumulating Tln appeared to cause a local distortion of the actin cytoskeleton.
Esselens et al. (2004) found that cultured Ps1 -/- mouse hippocampal neurons showed increased amounts of Tln protein and accumulation of Tln in phagocytic vacuoles distinct from classic autophagic vacuoles. Both the increased amount of Tln and Tln accumulation were independent of Ps1 gamma-secretase activity, since expression of dominant-negative human PS1 mutants in Ps1 -/- cells reversed both defects. Esselens et al. (2004) suggested that PS1 may have a role in targeting phagocytic vacuoles for lysosomal degradation.
Lindsberg et al. (2002) studied ICAM5 expression in the CSF of patients with acute encephalitis and found an increase in soluble ICAM5, which has a molecular weight of 115 kD. They postulated that the soluble protein is cleaved from the intact molecule present in human neurons during inflammation in the cerebral tissue. They noted that soluble ICAM5 levels in the CSF were increased whether or not epileptic seizure activity was present and suggested that the increase is related to immune factors rather than to epileptic activity. Lindsberg et al. (2002) suggested a role for the adhesion molecule in promoting host immune response and leukocyte recruitment into areas of potential microbial neuroinvasion.
By fluorescence in situ hybridization, Mizuno et al. (1997) mapped the TLCN gene to 19p13.2, in the proximity of ICAM1 (147840), ICAM3, and ICAM4.
Annaert, W. G., Esselens, C., Baert, V., Boeve, C., Snellings, G., Cupers, P., Craessaerts, K., De Strooper, B. Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins. Neuron 32: 579-589, 2001. [PubMed: 11719200] [Full Text: https://doi.org/10.1016/s0896-6273(01)00512-8]
Esselens, C., Oorschot, V., Baert, V., Raemaekers, T., Spittaels, K., Serneels, L., Zheng, H., Saftig, P., De Strooper, B., Klumperman, J., Annaert, W. Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway. J. Cell Biol. 166: 1041-1054, 2004. [PubMed: 15452145] [Full Text: https://doi.org/10.1083/jcb.200406060]
Lindsberg, P. J., Launes, J., Tian, L., Valimaa, H., Subramanian, V., Siren, J., Hokkanen, L., Hyypia, T., Carpen, O., Gahmberg, C. G. Release of soluble ICAM-5, a neuronal adhesion molecule, in acute encephalitis. Neurology 58: 446-451, 2002. [PubMed: 11839847] [Full Text: https://doi.org/10.1212/wnl.58.3.446]
Mizuno, T., Yoshihara, Y., Inazawa, J., Kagamiyama, H., Mori, K. cDNA cloning and chromosomal localization of the human telencephalin and its distinctive interaction with lymphocyte function-associated antigen-1. J. Biol. Chem. 272: 1156-1163, 1997. [PubMed: 8995416] [Full Text: https://doi.org/10.1074/jbc.272.2.1156]
Rieckmann, P., Turner, T., Kilgannon, P., Steinhoff, B. J. Telencephalin as an indicator for temporal-lobe dysfunction. Lancet 352: 370-371, 1998. [PubMed: 9717930] [Full Text: https://doi.org/10.1016/s0140-6736(05)60469-2]
Yoshihara, Y., Mori, K. Telencephalin: a neuronal area code molecule? Neurosci. Res. 21: 119-124, 1994. [PubMed: 7724062] [Full Text: https://doi.org/10.1016/0168-0102(94)90153-8]
Yoshihara, Y., Oka, S., Nemoto, Y., Watanabe, Y., Nagata, S., Kagamiyama, H., Mori, K. An ICAM-related neuronal glycoprotein, telencephalin, with brain segment-specific expression. Neuron 12: 541-553, 1994. [PubMed: 7794412] [Full Text: https://doi.org/10.1016/0896-6273(94)90211-9]