The Shortest Isoform of Dystrophin (Dp40) Interacts with a Group of Presynaptic Proteins to Form a Presumptive Novel Complex in the Mouse Brain

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2012 Jan 20

PMID 22258561

Citations 23

Authors

Takenori Tozawa

Kyoko Itoh

Takeshi Yaoi

So Tando

Masafumi Umekage

Hongmei Dai

Hajime Hosoi

Shinji Fushiki

Affiliations

Soon will be listed here.

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.

Citing Articles

Characterization of Dystrophin Dp71 Expression and Interaction Partners in Embryonic Brain Development: Implications for Duchenne/Becker Muscular Dystrophy.

Fujimoto T, Mori M, Tonosaki M, Yaoi T, Nakano K, Okamura T Mol Neurobiol. 2025; .

PMID: 39760982 DOI: 10.1007/s12035-024-04676-6.

Learning, memory and blood-brain barrier pathology in Duchenne muscular dystrophy mice lacking Dp427, or Dp427 and Dp140.

Verhaeg M, Adamzek K, van de Vijver D, Putker K, Engelbeen S, Wijnbergen D Genes Brain Behav. 2024; 23(3):e12895.

PMID: 38837620 PMC: 11151035. DOI: 10.1111/gbb.12895.

Dystrophin- and Utrophin-Based Therapeutic Approaches for Treatment of Duchenne Muscular Dystrophy: A Comparative Review.

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Dystrophin genetic variants and autism.

Passos-Bueno M, Costa C, Zatz M Discov Ment Health. 2023; 2(1):4.

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Nuclear Small Dystrophin Isoforms during Muscle Differentiation.

Donandt T, Todorow V, Hintze S, Graupner A, Schoser B, Walter M Life (Basel). 2023; 13(6).

PMID: 37374149 PMC: 10302385. DOI: 10.3390/life13061367.

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