Disease relevance of ICAM5

• A variant in ICAM5 was also associated with disease progression and prognosis [1].
• Although genetic variants in ICAM5 showed the strongest association with disease status, ICAM1 is expressed at highest levels in normal and tumor breast tissue [1].
• Our results replicate previous findings of association of the ICAM gene cluster with prostate cancer and suggest that common genetic variation within ICAM1 and not ICAM5 may be an important risk factor for prostate cancer [2].
• Release of soluble ICAM-5, a neuronal adhesion molecule, in acute encephalitis [3].
• In contrast, TLCN induced no significant change in morphology of neuroblastoma and fibroblasts [4].

Psychiatry related information on ICAM5

• Reduction of telencephalin immunoreactivity in the brain of patients with Alzheimer's disease [5].

High impact information on ICAM5

• Telencephalin as an indicator for temporal-lobe dysfunction [6].
• Absence of endosomal/lysosomal proteins suggests that the TLN-positive vacuoles fail to fuse with endosomes/lysosomes, preventing their acidification and further degradation [7].
• TLN mediates the uptake of microbeads concomitant with actin and PIP2 recruitment, indicating a phagocytic origin of TLN accumulations [7].
• Importantly, the TLN accumulations are suppressed by adenoviral expression of wild-type, FAD-linked and D257A mutant PS1, indicating that this phenotype is independent from gamma-secretase activity [7].
• Intercellular adhesion molecule-5 (ICAM-5) is a dendritically polarized membrane glycoprotein in telencephalic neurons, which shows heterophilic binding to leukocyte beta(2)-integrins [8].

Biological context of ICAM5

• High-density single nucleotide polymorphism mapping showed that the extent of association spans 20 kb and includes the intercellular adhesion molecule genes ICAM1, ICAM4, and ICAM5 [1].
• The TLN gene was mapped to the human chromosome 19p13.2, where the ICAM-1, -3, and -4 (LW) genes are located [9].
• Intercellular adhesion molecule 5 (ICAM-5, telencephalin) is a cell adhesion molecule expressed on neurons in the most rostral segment of the mammalian brain, the telencephalon [10].
• In addition, we report the mapping of the human ICAM-5 gene to an 80-kb region on chromosome 19p13.2 that also contains ICAM-1 and ICAM-3 [10].
• We studied here the binding site in ICAM-5 for CD11a/CD18 [11].

Anatomical context of ICAM5

• The neuronal glycoprotein telencephalin is a cellular ligand for the CD11a/CD18 leukocyte integrin [12].
• Telencephalin (TLN) is a novel member of the Ig superfamily expressed in the central nervous system [12].
• Peripheral blood T cells, Jurkat T cells, and B lymphoblastoid cells bound to immunopurified recombinant human TLN proteins [12].
• However, the interaction of TLN with LFA-1 on HL-60 cells was divalent cation-independent and phorbol 12-myristate 13-acetate stimulation-independent [9].
• These findings suggest that telencephalin identifies pyramidal neurons, it may identify plasma membrane as dendritic, and it may be generally adhesive or stabilize dendritic membranes, but it is probably not specifically synaptic [13].

Associations of ICAM5 with chemical compounds

• Human TLN comprises an NH2-terminal signal peptide, an extracellular region with nine Ig-like domains, a single transmembrane region, and a COOH-terminal cytoplasmic tail [9].
• We have extended this technique by the determination of high-resolution crystal structures of thermolysin (TLN), generated from crystals soaked in 2% to 100% isopropanol [14].
• We determined the high-resolution crystal structures of thermolysin (TLN), generated from crystals soaked in 50--70% acetone, 50--80% acetonitrile and 50 mM phenol [15].
• In view of the absence of effective treatment for patients with cerebral radionecrosis, alpha-tocopherol has the potential to be a complementary intervention for patients with cognitive dysfunction due to TLN [16].
• Because the C-terminal region of TLCN does not contain any canonical dendritic targeting sequences such as the tyrosine-based motif or the dileucine motif, this study suggests a novel mechanism of protein trafficking to the dendritic compartment of neurons [17].

Physical interactions of ICAM5

• Here, we demonstrate that TLN interacts with CD11a/CD18 [12].
• In summary, these results show that the interaction between ICAM-5 and alpha-actinin is mediated through binding of positively charged amino acids near the transmembrane domain of ICAM-5, and this interaction may play an important role in neuronal differentiation [18].

Other interactions of ICAM5

• The development of TLN was late compared to synaptophysin and microtubule-associated protein 2, suggesting its involvement in the functional maturation of neuronal dendrites and synapses [19].
• Besides its involvement in beta-catenin degradation, we discuss here the recent implication of presenilin 1 in the turnover of the intercellular cell adhesion molecule, telencephalin, through a degradation route that bears autophagic characteristics [20].
• One of the main proteins in the neuronal cell line Paju that bound to the ICAM-5 cytodomain was alpha-actinin [18].
• Treatment with the phosphatidylinositol 3'-kinase (PBK) inhibitor LY294002 resulted in ICAM-5 down-regulation [21].

Analytical, diagnostic and therapeutic context of ICAM5

• METHODS: The authors found, by immunoblotting, a 115-kDa soluble form of ICAM-5 (sICAM-5) cleaved from the membrane-bound (130 kDa) ICAM-5, and established an ELISA assay to measure it [3].
• METHODS: Twenty-nine patients with TLN after radiotherapy for NPC were recruited on a voluntary basis [16].
• We recently identified high ICAM-5 expression in a cDNA array study of head and neck neoplasms with a propensity for perineural invasion [21].

References