ALP exists primarily as two alternatively spliced variants; a 39.2 kDa (364 amino acids) protein in skeletal muscle and a 34.3 kDa (316 amino acids) protein in cardiac muscle and smooth muscle.[8][9][10] ALP has a N-terminal PDZ domain and a C-terminalLIM domain. In addition, the ALP subfamily contains a specific 34 amino acid domain named the ALP-like motif, containing protein kinase C consensus sequences.[11] The PDZ domain of ALP binds to alpha actinin-2, specifically to its spectrin-like repeats.[12] The PDZ domain is a motif composed of 80-120 amino acids with conserved four residue GLGF sequences that typically interact with C-termini of cytoskeletal proteins.[13] The region of heterogeneity in the two isoforms is between the PDZ domain and LIM domain.[10] ALP is localized to chromosome 4q35.[12] It has been shown that deletion of muscleblind-like 1 in mice can alter the splicing pattern of PDLIM3.[14]
Studies have shown that ALP is present at the first stage of myofibrilogenesis where it is bound to alpha actinin-2, and this association remains intact in mature myofibrils where ALP is localized to Z-discs and intercalated discs. Alpha actinin-2 is however not required for targeting ALP to Z-lines.[15] Studies in ALP knockout mice have shown that ALP facilitates the cross-linking of actin filaments by alpha actinin-2, and absence of ALP induces abnormal right ventricular chamber formation, dysplasia and cardiomyopathy.[16] Further studies using right ventricularepicardialsystolic strain and geometric remodeling analysis in these animals unveiled that absence of ALP diminishes right ventricular contractile function and alters the pattern of cardiac hypertrophic remodeling.[17] Two studies using integrative genomic approaches to investigate genetic modifiers of collagen deposition[18] or intrinsic aerobic running capacity (ARC)[19] have mapped PDLIM3 to respective quantitative trait loci, suggesting that ALP may be involved in molecular networks related to these cardiac phenomena.
Chromosome 4 pericentric inversion has been observed in 10 patients, with associated cardiac defects linked to terminal 4q35.1 deletions, which may affect PDLIM3.[20]
^Ponting CP, Phillips C (Mar 1995). "DHR domains in syntrophins, neuronal NO synthases and other intracellular proteins". Trends in Biochemical Sciences. 20 (3): 102–3. doi:10.1016/s0968-0004(00)88973-2. PMID7535955.
^Henderson JR, Pomiès P, Auffray C, Beckerle MC (Mar 2003). "ALP and MLP distribution during myofibrillogenesis in cultured cardiomyocytes". Cell Motility and the Cytoskeleton. 54 (3): 254–65. doi:10.1002/cm.10102. PMID12589684.
^ abPashmforoush M, Pomiès P, Peterson KL, Kubalak S, Ross J, Hefti A, Aebi U, Beckerle MC, Chien KR (May 2001). "Adult mice deficient in actinin-associated LIM-domain protein reveal a developmental pathway for right ventricular cardiomyopathy". Nature Medicine. 7 (5): 591–7. doi:10.1038/87920. PMID11329061. S2CID1781328.
^Lee SJ, Ways JA, Barbato JC, Essig D, Pettee K, DeRaedt SJ, Yang S, Weaver DA, Koch LG, Cicila GT (Sep 2005). "Gene expression profiling of the left ventricles in a rat model of intrinsic aerobic running capacity". Physiological Genomics. 23 (1): 62–71. CiteSeerX10.1.1.321.9888. doi:10.1152/physiolgenomics.00251.2004. PMID16033863.
^Maurin ML, Labrune P, Brisset S, Le Lorc'h M, Pineau D, Castel C, Romana S, Tachdjian G (Feb 2009). "Molecular cytogenetic characterization of a 4p15.1-pter duplication and a 4q35.1-qter deletion in a recombinant of chromosome 4 pericentric inversion". American Journal of Medical Genetics Part A. 149A (2): 226–31. doi:10.1002/ajmg.a.32603. PMID19161154. S2CID205310317.
Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Arola AM, Sanchez X, Murphy RT, Hasle E, Li H, Elliott PM, McKenna WJ, Towbin JA, Bowles NE (Apr 2007). "Mutations in PDLIM3 and MYOZ1 encoding myocyte Z line proteins are infrequently found in idiopathic dilated cardiomyopathy". Molecular Genetics and Metabolism. 90 (4): 435–40. doi:10.1016/j.ymgme.2006.12.008. PMID17254821.
French
Deutsch
