Absence of Dp71 in mdx3cv mouse spermatozoa alters flagellar morphology and the distribution of ion channels and nNOS

Abstract

In muscle, the absence of dystrophin alters the dystrophin-associated protein complex (DAPC), which is involved in the clustering and anchoring of signaling proteins and ion and water channels. Here we show that mice spermatozoa express only dystrophin Dp71 and utrophin Up71. The purpose of this study was to explore the effect of the absence of Dp71 on the morphology and membrane distribution of members of the DAPC, ion channels and signaling proteins of spermatozoa obtained from dystrophic mutant mdx3cv mice. Our work indicates that although the absence of Dp71 results in a dramatic decrease in β-dystroglycan, it induces membrane redistribution and an increase in the total level of α-syntrophin, voltage-dependent Na+ (μ1) and K+ (Kv1.1) channels and neural nitric oxide synthase (nNOS). The short utrophin (Up71) was upregulated and redistributed in the spermatozoa of mdx3cv mice. A significant increase in abnormal flagella morphology was observed in the absence of Dp71, which was partially corrected when the plasma membrane was eliminated by detergent treatment. Our observations point to a new phenotype associated with the absence of Dp71. Abnormal flagellar structure and altered distribution of ion channels and signaling proteins may be responsible for the fertility problems of mdx3cv mice.

Kir4.1 and AQP4 associate with Dp71‐ and utrophin‐DAPs complexes in specific and defined microdomains of Müller retinal glial cell membrane

“…Comparison of DAPs expression in utrophin-null and mdx 3cv mice strains reveals disruption, respectively, of the choroid plexus-utrophin dependent, and the glial cell-Dp71 dependent complexes with a loss of AQP4 channel in the glial end-feet, and no compensation for the missing protein by its homologous. In addition to the fact that utrophin is a well-known dystrophin-related protein with broad tissue distribution that performs similar cellular functions in association with the DAPs (Blake et al, 2002) and that it is upregulated when dystrophin is absent (Dalloz et al, 2001;Galvagni et al, 2002), the observed upregulation and redistribution of utrophin in Dp71-null M€ uller cells strongly suggest that it might compensate for Dp71 absence, as reported in mdx 3cv mice spermatozoa (Hernandez-Gonzalez et al, 2005) and platelet (Cerecedo et al, 2008).…”

“…8). It is interesting to note that recent work in mouse spermatozoa (Hernandez-Gonzalez et al, 2005) and platelets (Cerecedo et al, 2006) reported that these cells express Dp71 as well as utrophin Up71 and utrophin. In mdx 3cv mice, the drastic reduction of Dp71 expression induces a decrease of the expression of b-dystroglycan and an increase of utrophins in both cell types, as well as redistribution of members of the DAPs complex.…”

Cardiac Sodium Channel Na v 1.5 Is Regulated by a Multiprotein Complex Composed of Syntrophins and Dystrophin

“…17,18 In contrast, it should be noted that Na v channel expression in spermatozoa has been shown to be increased when dystrophin is absent. 28 Furthermore, in ␣1-syntrophin-deficient mice, the abundance of Na v channels at the neuromuscular junction was not modified, whereas their localization was altered. 29 Altogether, these findings suggest that one of the possible roles of dystrophin is to stabilize specific ion channel proteins by unknown mechanisms (similarly to the other DPC proteins) in the plasma membrane.…”

Role of dystrophins and utrophins in platelet adhesion process

“…is the most abundant protein product of the DMD gene in non-muscle tissues (Hugnot et al, 1992;Lederfein et al, 1992;Claudepierre et al, 1999, Hernández-González et al, 2005. Dp71d is the isoform of 76 kDa in which exon 78 is present, while the protein of 58 kDa has been designated as Dp71D 110 and is generated from Dp71 transcripts lacking exons 71-74 (Austin et al, 1995).…”