Proteopedia

Group:MUZIC:Tritopodin

Prediction of the PDZ binding domain of Tritopodin . Lambert et al. ESyPred3D:Prediction of Proteins 3D structures. Bioinformatics 2002)

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IntroductionIntroduction

Tritopodin is the third member (besides myopodin and synaptopodin) of the podin family proteins and is codified by the gene SYNPO2L[1]. Tritopodin has been revealed by database searches, and since it is the third member of the podin family of proteins with extended sequence similarity, was named ‘‘tritopodin’’. Trotopodin is also known under the names synaptopodin 2-like, Myopodin-like and CHAP (cytoskeletal heart-enriched actin-associated protein) and is found in heart and skeletal muscle tissue [1].

Sequence AnnotationSequence Annotation

Tritopodin share 33% of homology in the Aminoacid sequence with Myopodin and 30% with Synaptopodin [2], which makes believe similar functions for both proteins. The human gene SYNPO2L-Gen, that codifies for Tritopodin it is form by 5 exons, which are separated by different large introns. Database Analysis (UCSC Genome Browser, EMBL) predicted 2 putative differential splicing sequence. Splicing sequence 1 lead to of the 4th Exons, while the intraexon splicing sequence 2 lead to the loss of the central portion of the 5th exon. From these splicing sequence and an alternative transcription start were predicted 2 isoforms: Tritopodin a (in human 102.5kDa and in mouse 103.3kDa see figure) and Tritopodin b (in both human and mouse 79kDa). After running SDS gel, Beqqali et al. postulated 2 isoforms: mCHAPa from exon 1,2,3 and 5, as well as mCHAPb that result from a start-codon in exon 4, from which derives two proteins variants of 140kDa (mCHAPa) and 110kDa (mCHAPb) [3].


 

FunctionFunction

Tritopodin is expressed in vivo and in vitro in differentiated skeletal- and heart muscle cells, associates with polymerized actin, and is conserved amongst vertebrates, indicating an essential role in muscle function. Furthermore Tritopodin is able to translocate to the nucleus, and plays an important role in skeletal and cardiac muscle development. [4] [5].


Tritopodin InteractionsTritopodin Interactions

Tritopodin and Myopodin localizes in the sarcomeric Z-disc, where they interact with α-actinin, verify by CoIPs and yeast two-hybrid assays [6]. Adult skeletal and heart tissue shows the colocalization from mCHAP with α-actinin in the sarcomeric Z-disc and in the nucleus in embrional Cardiomyocytes [7].

PathologyPathology

ReferencesReferences

  1. ↑ Claeys KG, van der Ven PF, Behin A, Stojkovic T, Eymard B, Dubourg O, Laforet P, Faulkner G, Richard P, Vicart P, Romero NB, Stoltenburg G, Udd B, Fardeau M, Voit T, Furst DO. Differential involvement of sarcomeric proteins in myofibrillar myopathies: a morphological and immunohistochemical study. Acta Neuropathol. 2009 Mar;117(3):293-307. Epub 2009 Jan 17. PMID:19151983 doi:10.1007/s00401-008-0479-7
  2. ↑ Mundel P, Heid HW, Mundel TM, Kruger M, Reiser J, Kriz W. Synaptopodin: an actin-associated protein in telencephalic dendrites and renal podocytes. J Cell Biol. 1997 Oct 6;139(1):193-204. PMID:9314539
  3. ↑ Beqqali A, Monshouwer-Kloots J, Monteiro R, Welling M, Bakkers J, Ehler E, Verkleij A, Mummery C, Passier R. CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function. J Cell Sci. 2010 Apr 1;123(Pt 7):1141-50. Epub 2010 Mar 9. PMID:20215401 doi:10.1242/jcs.063859
  4. ↑ Linnemann A, van der Ven PF, Vakeel P, Albinus B, Simonis D, Bendas G, Schenk JA, Micheel B, Kley RA, Furst DO. The sarcomeric Z-disc component myopodin is a multiadapter protein that interacts with filamin and alpha-actinin. Eur J Cell Biol. 2010 Sep;89(9):681-92. Epub 2010 May 31. PMID:20554076 doi:10.1016/j.ejcb.2010.04.004
  5. ↑ Beqqali A, Monshouwer-Kloots J, Monteiro R, Welling M, Bakkers J, Ehler E, Verkleij A, Mummery C, Passier R. CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function. J Cell Sci. 2010 Apr 1;123(Pt 7):1141-50. Epub 2010 Mar 9. PMID:20215401 doi:10.1242/jcs.063859
  6. ↑ Linnemann A, van der Ven PF, Vakeel P, Albinus B, Simonis D, Bendas G, Schenk JA, Micheel B, Kley RA, Furst DO. The sarcomeric Z-disc component myopodin is a multiadapter protein that interacts with filamin and alpha-actinin. Eur J Cell Biol. 2010 Sep;89(9):681-92. Epub 2010 May 31. PMID:20554076 doi:10.1016/j.ejcb.2010.04.004
  7. ↑ Beqqali A, Monshouwer-Kloots J, Monteiro R, Welling M, Bakkers J, Ehler E, Verkleij A, Mummery C, Passier R. CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function. J Cell Sci. 2010 Apr 1;123(Pt 7):1141-50. Epub 2010 Mar 9. PMID:20215401 doi:10.1242/jcs.063859
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