title: The shortest isoform of dystrophin (Dp40) interacts with a group of presynaptic proteins to form a presumptive novel complex in the mouse brain.
abstract: Duchenne muscular dystrophy (DMD) causes cognitive impairment in one third of the patients, although the underlying mechanisms remain to be elucidated. Recent studies showed that mutations in the distal part of the dystrophin gene correlate well with the cognitive impairment in DMD patients, which is attributed to Dp71. The study on the expression of the shortest isoform, Dp40, has not been possible due to the lack of an isoform specific antibody. Dp40 has the same promoter as that found in Dp71 and lacks the normal C-terminal end of Dp427. In the present study, we have raised polyclonal antibody against the N-terminal sequence common to short isoforms of dystrophin, including Dp40, and investigated the expression pattern of Dp40 in the mouse brain. Affinity chromatography with this antibody and the consecutive LC-MS/MS analysis on the interacting proteins revealed that Dp40 was abundantly expressed in synaptic vesicles and interacted with a group of presynaptic proteins, including syntaxin1A and SNAP25, which are involved in exocytosis of synaptic vesicles in neurons. We thus suggest that Dp40 may form a novel protein complex and play a crucial role in presynaptic function. Further studies on these aspects of Dp40 function might provide more insight into the molecular mechanisms of cognitive impairment found in patients with DMD.
authors.affiliation: Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Tozawa
authors.forename: Kyoko
authors.initials: K
authors.lastname: Itoh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yaoi
authors.forename: So
authors.initials: S
authors.lastname: Tando
authors.forename: Masafumi
authors.initials: M
authors.lastname: Umekage
authors.forename: Hongmei
authors.initials: H
authors.lastname: Dai
authors.forename: Hajime
authors.initials: H
authors.lastname: Hosoi
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiki
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D016189:Dystrophin / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D020388:Muscular Dystrophy, Duchenne / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D016189:Dystrophin; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms