Drosophila stathmin: a microtubule-destabilizing factor involved in nervous system formation.
Stathmin is a ubiquitous regulatory phosphoprotein, the generic element of a family of neural phosphoproteins in vertebrates that possess the capacity to bind tubulin and interfere with microtubule dynamics. Although stathmin and the other proteins of the family have been associated with numerous cell regulations, their biological roles remain elusive, as in particular inactivation of the stathmin gene in the mouse resulted in no clear deleterious phenotype. We identified stathmin phosphoproteins in Drosophila, encoded by a unique gene sharing the intron/exon structure of the vertebrate stathmin and stathmin family genes. They interfere with microtubule assembly in vitro, and in vivo when expressed in HeLa cells. Drosophila stathmin expression is regulated during embryogenesis: it is high in the migrating germ cells and in the central and peripheral nervous systems, a pattern resembling that of mammalian stathmin. Furthermore, RNA interference inactivation of Drosophila stathmin expression resulted in germ cell migration arrest at stage 14. It also induced important anomalies in nervous system development, such as loss of commissures and longitudinal connectives in the ventral cord, or abnormal chordotonal neuron organization. In conclusion, a single Drosophila gene encodes phosphoproteins homologous to the entire vertebrate stathmin family. We demonstrate for the first time their direct involvement in major biological processes such as development of the reproductive and nervous systems.
Ozon
Sylvie
S
Institut National de la Santé et de la Recherche Médicale U440-Université Pierre et Marie Curie, Institut du Fer à Moulin, 75005 Paris, France.
Guichet
Antoine
A
Gavet
Olivier
O
Roth
Siegfried
S
Sobel
André
A
D000595:Amino Acid Sequence; D000818:Animals; D004330:Drosophila / Q000196:embryology / Q000502:physiology*; D005091:Exons / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008868:Microtubule Proteins; D008870:Microtubules / Q000502:physiology*; D008969:Molecular Sequence Data; D009420:Nervous System / Q000196:embryology*; D010750:Phosphoproteins / Q000502:physiology*; D050777:Stathmin; D014162:Transfection
D008868:Microtubule Proteins; D010750:Phosphoproteins; C493995:STMN1 protein, human; D050777:Stathmin