Essential roles of LEM-domain protein MAN1 during organogenesis in Xenopus laevis and overlapping functions of emerin

Eur J Cell Biol. Aug-Sep 2013;92(8-9):280-94. doi: 10.1016/j.ejcb.2013.10.008. Epub 2013 Nov 1.

Abstract

Mutations in nuclear envelope proteins are linked to an increasing number of human diseases, called envelopathies. Mutations in the inner nuclear membrane protein emerin lead to X-linked Emery-Dreifuss muscular dystrophy, characterized by muscle weakness or wasting. Conversely, mutations in nuclear envelope protein MAN1 are linked to bone and skin disorders. Both proteins share a highly conserved domain, called LEM-domain. LEM proteins are known to interact with Barrier-to-autointegration factor and several transcription factors. Most envelopathies are tissue-specific, but knowledge on the physiological roles of related LEM proteins is still unclear. For this reason, we investigated the roles of MAN1 and emerin during Xenopus laevis organogenesis. Morpholino-mediated knockdown of MAN1 revealed that MAN1 is essential for the formation of eye, skeletal and cardiac muscle tissues. The MAN1 knockdown could be compensated by ectopic expression of emerin, leading to a proper organ development. Further investigations revealed that MAN1 is involved in regulation of genes essential for organ development and tissue homeostasis. Thereby our work supports that LEM proteins might be involved in signalling essential for organ development during early embryogenesis and suggests that loss of MAN1 may cause muscle and retina specific diseases.

Keywords: Emerin; LEM-domain; MAN1; Nuclear envelope; Organogenesis; Xenopus laevis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Eye Abnormalities / embryology
  • Eye Abnormalities / metabolism
  • Female
  • Gene Knockdown Techniques
  • Heart Defects, Congenital / embryology
  • Heart Defects, Congenital / metabolism
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Muscle, Skeletal / abnormalities
  • Muscle, Skeletal / embryology
  • Muscle, Skeletal / metabolism
  • Mutation
  • Nuclear Envelope / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Organogenesis / physiology*
  • Protein Structure, Tertiary
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / abnormalities
  • Xenopus laevis / embryology*
  • Xenopus laevis / metabolism

Substances

  • LEMD3 protein, Xenopus
  • Membrane Proteins
  • Nuclear Proteins
  • Xenopus Proteins
  • emerin