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

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.

Ocular and neurodevelopmental features of Duchenne muscular dystrophy: a signature of dystrophin function in the central nervous system

“…Dp427, Dp260 and Dp140 are located in photoreceptor terminals, whereas Dp71 is expressed in Müller glia cells. [16][17][18][19][20] Recently, Dp427, Dp260 and Dp140 expressions have been identified in inner retinal layer neurons as well; Dp427 was expressed proportionately more at cone than rod synapses, in bipolar cells and some amacrine cells. 19 Mutations downstream of exon 30, which affect Dp260 expression, are associated with an abnormal scotopic electroretinogram (ERG) waveform [21][22][23][24] and some impairment of red-green colour vision.…”

Domain Wise Distribution of Mutations in Dystrophin Protein and Duchenne Muscular Dystrophy

“…Dp71 is not expressed in skeletal muscle tissues but is the major product in non-muscle tissues. Its immense importance reflects with the notation that this is present in embryonic stem cells and is the first gene product to be identified in developmental stage [30]. In our earlier works, we have gathered information from publicly available DMD database sources and have isolated 18 novel point mutation causing DMD in particular [31].…”

Dp71 gene disruption alters the composition of the dystrophin-associated protein complex and neuronal nitric oxide synthase expression in the hypothalamic supraoptic and paraventricular nuclei

“…The level of a1-Syn was lower in both the SON and PVN of Dp71-null mice than in wild-type mice and almost completely absent from around vessels, suggesting that the DAPC in the astrocyte end feet of the Dp71-null mice contained utrophins and b-DG but not a1-Syn. DAPC, via dystroglycans and SYN, constitutes a transmembrane system that connects the intracellular cytoskeleton to the extracellular matrix (Tadayoni et al 2012). Modification of the DAPC composition may thus have several consequences.…”

“…In the CNS, the DP71-associated DAPC is assembled through interactions among dystroglycan, a1-syntrophin (a1-Syn), and neuronal nitric oxide synthase (nNOS; Tadayoni et al 2012). Dystroglycan is a heterodimeric glycoprotein subcomplex located on the surfaces of cells in most adult tissues (Michele & Campbell 2003) and consists of a transmembrane b subunit and a noncovalently associated extracellular a subunit.…”