INVESTIGADORES
MARTIN Mauricio Gerardo
artículos
Título:
Sphingomyelin upregulation in mature neurons contributes to TrkB activity by Rac1 endocytosis
Autor/es:
LAURA TROVÓ; PAUL VAN VELDHOVEN; MAURICIO G MARTIN; CARLOS G DOTTI
Revista:
JOURNAL OF CELL SCIENCE
Editorial:
COMPANY OF BIOLOGISTS LTD
Referencias:
Año: 2011 vol. 124 p. 1308 - 1315
ISSN:
0021-9533
Resumen:
A developmentally regulated loss of membrane cholesterol was reported to
be sufficient and necessary for activation of neurotrophic
tyrosine kinase receptor type 2 (TrkB) in aged
neurons in vitro. However, TrkB activity in low cholesterol neurons
remains
confined to detergent-resistant membrane fractions,
indicating that additional lipidic changes occur with age. Analysis of
neuronal lipids at different developmental stages
revealed a sharp increase in sphingomyelin (SM) during neuronal
maturation.
Reduction of SM abrogated TrkB activation in mature
neurons, whereas increasing SM in immature neurons triggered receptor
activation. TrkB activity in high SM background was
the consequence of enhanced phosphorylation in the detergent-resistant
fractions and increased Rac1-mediated endocytosis.
The current results reveal developmental upregulation of SM as an
important
mechanism for sustaining TrkB activity in the
mature nervous system, in addition to the presence of brain-derived
neurotrophic
factor (BDNF).