Nuclear transport and subcellular localization of the dystrophin Dp71 and Dp40 isoforms in the PC12 cell line

Biochem Biophys Res Commun. 2022 Nov 19:630:125-132. doi: 10.1016/j.bbrc.2022.09.035. Epub 2022 Sep 13.

Abstract

The shortest dystrophins, Dp71 and Dp40, are transcribed from the DMD gene through an internal promoter located in intron 62. These proteins are the main product of the DMD gene in the nervous system and have been involved in various functions related to cellular differentiation and proliferation as well as other cellular processes. Dp71 mRNA undergoes alternative splicing that results in different Dp71 protein isoforms. The subcellular localization of some of these isoforms in the PC12 cell line has been previously reported, and a differential subcellular distribution was observed, which suggests a particular role for each isoform. With the aim of obtaining information on their function, this study identified factors involved in the nuclear transport of Dp71 and Dp40 isoforms in the PC12 cell line. Cell cultures were treated with specific nuclear import/export inhibitors to determine the Dp71 isoform transport routes. The results showed that all isoforms of Dp71 and Dp40 included in the analysis have the ability to enter the cell nucleus through α/β importin, and the main route of nuclear export for Dp71 isoforms is through the exportin CRM1, which is not the case for Dp40.

Keywords: Dystrophin Dp40; Dystrophin Dp71; Nuclear export; Nuclear import; PC12 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Dystrophin* / genetics
  • Dystrophin* / metabolism
  • Intracellular Space
  • Karyopherins / metabolism
  • PC12 Cells
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • beta Karyopherins* / metabolism

Substances

  • Dystrophin
  • Karyopherins
  • Protein Isoforms
  • RNA, Messenger
  • beta Karyopherins