ALP exists primarily as two alternatively spliced variants; a 39.2 kDa (364 amino acids)protein inskeletal muscle and a 34.3 kDa (316 amino acids)protein incardiac muscle andsmooth muscle.[8][9][10] ALP has aN-terminal PDZ domain and aC-terminalLIM domain. In addition, the ALP subfamily contains a specific 34amino acid domain named the ALP-like motif, containingprotein kinase C consensus sequences.[11] ThePDZ domain of ALP binds toalpha actinin-2, specifically to its spectrin-like repeats.[12] ThePDZ domain is a motif composed of 80-120 amino acids with conserved four residue GLGF sequences that typically interact withC-termini of cytoskeletal proteins.[13] The region of heterogeneity in the two isoforms is between thePDZ domain andLIM 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 ofPDLIM3.[14]
Studies have shown that ALP is present at the first stage of myofibrilogenesis where it is bound toalpha actinin-2, and this association remains intact in maturemyofibrils where ALP is localized toZ-discs andintercalated discs.Alpha actinin-2 is however not required for targeting ALP toZ-lines.[15] Studies in ALP knockout mice have shown that ALP facilitates the cross-linking ofactin filaments byalpha actinin-2, and absence of ALP induces abnormalright ventricular chamber formation,dysplasia andcardiomyopathy.[16] Further studies usingright ventricularepicardialsystolic strain and geometric remodeling analysis in these animals unveiled that absence of ALP diminishesright ventricular contractile function and alters the pattern ofcardiac 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 mappedPDLIM3 to respectivequantitative 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 affectPDLIM3.[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.
