INVESTIGADORES
ROSSO Silvana Beatriz
artículos
Título:
Regulation of membrane expansion at the nerve
Autor/es:
KARL H. PFENNINGER; LISANDRO LAURINO; DIEGO PERETTI; XIAOXIN WANG; SILVANA ROSSO; GERARDO MORFINI; ALFREDO CÁCERES; SANTIAGO QUIROGA
Revista:
JOURNAL OF CELL SCIENCE
Editorial:
COMPANY OF BIOLOGISTS LTD
Referencias:
Lugar: Cambridge; Año: 2003 vol. 116 p. 1209 - 1217
ISSN:
0021-9533
Resumen:
Exocytotic incorporation of plasmalemmal precursor
vesicles (PPVs) into the cell surface is necessary for neurite
extension and is known to occur mainly at the growth cone.
This report examines whether this is a regulated event
controlled by growth factors. The Golgi complex and
nascent PPVs of hippocampal neurons in culture were
pulse-labeled with fluorescent ceramide. We studied the
dynamics of labeled PPVs upon arrival at the axonal
growth cone. In controls and cultures stimulated with
brain-derived neurotrophic factor (BDNF), PPV clusters
persisted in growth cones with a half-life (t1/2) of >14
minutes. Upon challenge with IGF-1, however, fluorescent
elements cleared from the growth cones with a t1/2 of only
6 minutes. Plasmalemmal expansion was measured directly
as externalization of membrane glycoconjugates in resealed
growth cone particles (GCPs) isolated from fetal forebrain.
These assays demonstrated that membrane expansion
could be stimulated by IGF-1 in a dose-dependent manner
but not by BDNF, even though intact, functional BDNF
receptor was present on GCPs. Because both BDNF and
IGF-1 are known to enhance neurite growth, but BDNF did
not stimulate membrane expansion at the growth cone, we
studied the effect of BDNF on the IGF-1 receptor. BDNF
was found to cause the translocation of the growth-conespecific
IGF-1 receptor subunit bgc to the distal axon, in
a KIF2-dependent manner. We conclude that IGF-1
stimulates axonal assembly at the growth cone, and that
this occurs via regulated exocytosis of PPVs. This
mechanism is affected by BDNF only indirectly, by
regulation of the bgc level at the growth cone.t1/2) of >14
minutes. Upon challenge with IGF-1, however, fluorescent
elements cleared from the growth cones with a t1/2 of only
6 minutes. Plasmalemmal expansion was measured directly
as externalization of membrane glycoconjugates in resealed
growth cone particles (GCPs) isolated from fetal forebrain.
These assays demonstrated that membrane expansion
could be stimulated by IGF-1 in a dose-dependent manner
but not by BDNF, even though intact, functional BDNF
receptor was present on GCPs. Because both BDNF and
IGF-1 are known to enhance neurite growth, but BDNF did
not stimulate membrane expansion at the growth cone, we
studied the effect of BDNF on the IGF-1 receptor. BDNF
was found to cause the translocation of the growth-conespecific
IGF-1 receptor subunit bgc to the distal axon, in
a KIF2-dependent manner. We conclude that IGF-1
stimulates axonal assembly at the growth cone, and that
this occurs via regulated exocytosis of PPVs. This
mechanism is affected by BDNF only indirectly, by
regulation of the bgc level at the growth cone.t1/2 of only
6 minutes. Plasmalemmal expansion was measured directly
as externalization of membrane glycoconjugates in resealed
growth cone particles (GCPs) isolated from fetal forebrain.
These assays demonstrated that membrane expansion
could be stimulated by IGF-1 in a dose-dependent manner
but not by BDNF, even though intact, functional BDNF
receptor was present on GCPs. Because both BDNF and
IGF-1 are known to enhance neurite growth, but BDNF did
not stimulate membrane expansion at the growth cone, we
studied the effect of BDNF on the IGF-1 receptor. BDNF
was found to cause the translocation of the growth-conespecific
IGF-1 receptor subunit bgc to the distal axon, in
a KIF2-dependent manner. We conclude that IGF-1
stimulates axonal assembly at the growth cone, and that
this occurs via regulated exocytosis of PPVs. This
mechanism is affected by BDNF only indirectly, by
regulation of the bgc level at the growth cone.bgc to the distal axon, in
a KIF2-dependent manner. We conclude that IGF-1
stimulates axonal assembly at the growth cone, and that
this occurs via regulated exocytosis of PPVs. This
mechanism is affected by BDNF only indirectly, by
regulation of the bgc level at the growth cone.bgc level at the growth cone.