Expression of stathmin, a developmentally controlled cytoskeleton-regulating molecule, in demyelinating disorders.
Understanding the biological relevance of reexpression of developmental molecules in pathological conditions is crucial for the development of new therapies. In this study, we report the increased expression of stathmin, a developmentally regulated tubulin-binding protein, in the brains of patients with multiple sclerosis (MS). In physiological conditions, stathmin immunoreactivity was observed in polysialic acid-neural cell adhesion molecule-positive migratory progenitors in the subventricular zone, and its expression progressively decreased as the cells matured into oligodendrocytes (OLs). In MS patients, however, stathmin levels were elevated in 2',3'-cyclic nucleotide 3'-phosphodiesterase-positive OLs, in 10 of 10 bioptic samples analyzed. Increased levels of stathmin were confirmed by Western blot analysis of normal-appearing white matter samples from MS brains. In addition, using mass spectrometry, stathmin was identified as the main component of a specific myelin protein fraction consistently increased in MS preparations compared with controls. To test the biological relevance of increased stathmin levels, primary OL progenitors were transfected using a myc-tagged stathmin cDNA and were allowed to differentiate. Consistent with a distinct role played by this molecule in cells of the OL lineage at different developmental stages, transient transfection in progenitors favored the bipolar migratory phenotype but did not affect survival. However, sustained stathmin levels in differentiating OLs, because of overexpression, resulted in enhanced apoptotic susceptibility. We conclude that stathmin expression in demyelinating disorders could have a dual role. On one hand, by favoring the migratory phenotype of progenitors, it may promote myelin repair. On the other hand, stathmin in mature OLs may indicate cell stress and possibly affect survival.
Liu
Aixiao
A
Department of Neuroscience, R. Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Stadelmann
Christine
C
Moscarello
Mario
M
Bruck
Wolfgang
W
Sobel
Andre'
A
Mastronardi
Fabrizio G
FG
Casaccia-Bonnefil
Patrizia
P
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism*; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism; D004996:Ethidium; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008868:Microtubule Proteins / Q000096:biosynthesis* / Q000502:physiology; D009103:Multiple Sclerosis / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000502:physiology; D051381:Rats; D050777:Stathmin; D013234:Stem Cells / Q000378:metabolism
D008868:Microtubule Proteins; D010750:Phosphoproteins; C493995:STMN1 protein, human; D050777:Stathmin; C493994:Stmn1 protein, mouse; D004996:Ethidium