title: Identification of a novel muscle A-type lamin-interacting protein (MLIP).
abstract: Mutations in the A-type lamin (LMNA) gene are associated with age-associated degenerative disorders of mesenchymal tissues, such as dilated cardiomyopathy, Emery-Dreifuss muscular dystrophy, and limb-girdle muscular dystrophy. The molecular mechanisms that connect mutations in LMNA with different human diseases are poorly understood. Here, we report the identification of a Muscle-enriched A-type Lamin-interacting Protein, MLIP (C6orf142 and 2310046A06rik), a unique single copy gene that is an innovation of amniotes (reptiles, birds, and mammals). MLIP encodes alternatively spliced variants (23-57 kDa) and possesses several novel structural motifs not found in other proteins. MLIP is expressed ubiquitously and most abundantly in heart, skeletal, and smooth muscle. MLIP interacts directly and co-localizes with lamin A and C in the nuclear envelope. MLIP also co-localizes with promyelocytic leukemia (PML) bodies within the nucleus. PML, like MLIP, is only found in amniotes, suggesting that a functional link between the nuclear envelope and PML bodies may exist through MLIP. Down-regulation of lamin A/C expression by shRNA results in the up-regulation and mislocalization of MLIP. Given that MLIP is expressed most highly in striated and smooth muscle, it is likely to contribute to the mesenchymal phenotypes of laminopathies.
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Elmira
authors.initials: E
authors.lastname: Ahmady
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Deeke
authors.forename: Seham
authors.initials: S
authors.lastname: Rabaa
authors.forename: Lara
authors.initials: L
authors.lastname: Kouri
authors.forename: Laura
authors.initials: L
authors.lastname: Kenney
authors.forename: Alexandre F R
authors.initials: AF
authors.lastname: Stewart
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Burgon
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D056970:Co-Repressor Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D056970:Co-Repressor Proteins; D034904:Lamin Type A; C559899:MLIP protein, mouse; D009124:Muscle Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins