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Dystrophin Dp71: The Smallest but Multifunctional Product of the Duchenne Muscular Dystrophy Gene

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Abstract

Dystrophin Dp71 is expressed in all tissues, with the exception of skeletal muscle, and is the main Duchenne muscular dystrophy (DMD) gene product in brain. As full-length dystrophin does in skeletal muscle, Dp71 associates with dystroglycans, sarcoglycans, dystrobrevins, syntrophins, and accessory proteins to form the dystrophin-associated protein complex (DAPC) in non-muscle tissues. Although it has been nearly 20 years since the discovery of Dp71, its study has become relevant only recently due to its direct involvement with the two main DMD non-muscular phenotypes: cognitive impairment and abnormal retinal physiology. In this review, we describe the historical background of Dp71 and the experimental models developed for its study. Additionally, we present and discuss the experimental evidence supporting the participation of Dp71 in different cellular processes, including cell adhesion, water homeostasis, cell division, and nuclear architecture. The functional diversity of Dp71 is attributed to the formation of Dp71-containing DAPC in numerous cell types and different subcellular compartments, including in plasma membrane and nucleus, as well as to the capability of Dp71-containing DAPC to work as the scaffold for proper clustering and anchoring of structural and signaling proteins to the plasma membrane and of nuclear envelope proteins to the inner nuclear membrane.

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Abbreviations

DMD:

Duchenne muscular dystrophy

DAPC:

Dystrophin-associated protein complex

PCR:

Polymerase chain reaction

cDNA:

Complementary DNA

Cre-loxP:

Recombination system based on Cre site-specific DNA recombinase and loxP DNA sequences

Bgeo :

β-Galactosidase–neomycin-resistant gene fusion

mdx :

Mouse with X chromosome-linked muscular dystrophy

cAMP:

Cyclic adenosine monophosphate

NGF:

Nerve growth factor

Sp1:

Specificity protein 1

Na+ :

Sodium ion

K+ :

Potassium ion

AP2α:

Activating protein 2α

NLS:

Nuclear localization signal

IQ:

Intelligence quotient

LTP:

Long-term potentiation

LTD:

Long-term depression

ERG:

Electroretinogram

AMPAr:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

NMDAr:

N-methyl-d-aspartate receptor

OPL:

Outer plexiform layer

Kir4.1:

Inwardly rectifying potassium channels 4.1

AQP4:

Water transport protein pore aquaporin-4

FAK:

Focal adhesion kinase

BRB:

Blood–retinal barrier

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Acknowledgments

This work was supported by CONACyT-México, grant no. 128418 (B.C.), the Association Française contre les Myopathies (AFM), INSERM (A.R.), Alcon France Laboratories, and Alain Gaudric, MD (R.T.).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Ophthalmology Department, Hôpital Lariboisière, AP-HP, Université Paris Diderot, Paris, France

    Ramin Tadayoni

  2. Institut de la Vision, INSERM UMR_S968, CNRS UMR_7210, Université Pierre et Marie Curie Paris 06, 17 rue Moreau, Paris, 75012, France

    Ramin Tadayoni & Alvaro Rendon

  3. Área Académica de Medicina, I.C.Sa., Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, México

    L. E. Soria-Jasso

  4. Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados—Instituto Politécnico Nacional (CINVESTAV-IPN), México Distrito Federal, México

    Bulmaro Cisneros

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  1. Ramin Tadayoni
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  2. Alvaro Rendon
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  3. L. E. Soria-Jasso
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  4. Bulmaro Cisneros
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Correspondence to Bulmaro Cisneros.

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Ramin Tadayoni and Alvaro Rendon contributed equally to this work.

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Tadayoni, R., Rendon, A., Soria-Jasso, L.E. et al. Dystrophin Dp71: The Smallest but Multifunctional Product of the Duchenne Muscular Dystrophy Gene. Mol Neurobiol 45, 43–60 (2012). https://doi.org/10.1007/s12035-011-8218-9

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