title: Multiple novel nesprin-1 and nesprin-2 variants act as versatile tissue-specific intracellular scaffolds.
abstract: BACKGROUND
  Nesprins (Nuclear envelope spectrin-repeat proteins) are a novel family of giant spectrin-repeat containing proteins. The nesprin-1 and nesprin-2 genes consist of 146 and 116 exons which encode proteins of ∼1mDa and ∼800 kDa is size respectively when all the exons are utilised in translation. However emerging data suggests that the nesprins have multiple alternative start and termination sites throughout their genes allowing the generation of smaller isoforms.
  
  
  RESULTS
  In this study we set out to identify novel alternatively transcribed nesprin variants by screening the EST database and by using RACE analysis to identify cDNA ends. These two methods provided potential hits for alternative start and termination sites that were validated by PCR and DNA sequencing. We show that these alternative sites are not only expressed in a tissue specific manner but by combining different sites together it is possible to create a wide array of nesprin variants. By cloning and expressing small novel nesprin variants into human fibroblasts and U2OS cells we show localization to actin stress-fibres, focal adhesions, microtubules, the nucleolus, nuclear matrix and the nuclear envelope (NE). Furthermore we show that the sub-cellular localization of individual nesprin variants can vary depending on the cell type, suggesting any single nesprin variant may have different functions in different cell types.
  
  
  CONCLUSIONS
  These studies suggest nesprins act as highly versatile tissue specific intracellular protein scaffolds and identify potential novel functions for nesprins beyond cytoplasmic-nuclear coupling. These alternate functions may also account for the diverse range of disease phenotypes observed when these genes are mutated.
authors: Cardiovascular Division, James Black Centre, King's College London, London, United Kingdom.
authors: Dipen
authors: D
authors: Rajgor
authors: Jason A
authors: JA
authors: Mellad
authors: Flavia
authors: F
authors: Autore
authors: Qiuping
authors: Q
authors: Zhang
authors: Catherine M
authors: CM
authors: Shanahan
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity / Q000502:physiology; D022502:Stress Fibers / Q000235:genetics / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C415465:SYNE1 protein, human; C485904:SYNE2 protein, human