ALVAREZ CECILIA INÉS
Congresos y reuniones científicas
Título:
Role of CREB3 transcription factors in neuronal differentiation models
Autor/es:
SAMPIERI, L; FUNES CHABÁN, MACARENA; ROZÉS-SALVADOR, VICTORIA; ALVAREZ, CECILIA
Lugar:
Santa Cruz
Reunión:
Workshop; EMBO Workshop Emerging Concepts of the Neuronal Cytoskeleton; 2023
Institución organizadora:
IUBMB EMBO
Resumen:
Neuronal processes such as growth and differentiation demand extensive membrane remodeling and
protein redistribution. Formation of new neuritic processes required the adaptation of the secretory
pathway, which is regulated, in multiple cell types, by members of the CREB3 family of transcription
factors. CREB3 factors have emerged as signaling hubs for the regulation of Golgi homeostasis,
integrating stimuli to control cellular events that impact membrane expansion and composition.
Although recent studies have focused on their role in the central nervous system, little is known about
CREB3 factors in neuronal differentiation. Here, we analyze the expression of CREB3 family members
using two models: i) NGF-induced PC12 cell differentiation and ii) differentiation of embryonic rat
hippocampal neurons. The results show that NGF treatment or developing hippocampal neurons
increases the expression of some proteins necessary for membrane transport (transport factors). In
addition, a significant increase in CREB3L2 mRNA and protein levels is detected in response to NGF,
and expression of both CREB3L1 and CREB3L2 increase in hippocampal neurons (1-7DIV).
Interestingly, CREB3L2-overexpression hampers NGF-induced neurite outgrowth, while its inhibition
enhances it. Consistent with this, CREB3L2-overexpressing PC12 cells show higher expression of
GTPase Rab5 (a negative regulator of PC12 differentiation) than control cells. In contrast, in
hippocampal neurons, CREB3L1 expression is higher than CREB3L2, and overexpression of a
CREB3L1 dominant negative construct reduces axonal growth and increases Golgi fragmentation,
compared to controls. Taken together, our findings strongly suggest that CREB3 factors are involved in
neuronal differentiation by modulating the adaptation of the secretory pathway.
Financing: PICT 2019-1625, BID from the Ministry of Science and Technology of Argentina and SECyT-UNC (2018–2021) from Universidad
Nacional de Córdoba
protein redistribution. Formation of new neuritic processes required the adaptation of the secretory
pathway, which is regulated, in multiple cell types, by members of the CREB3 family of transcription
factors. CREB3 factors have emerged as signaling hubs for the regulation of Golgi homeostasis,
integrating stimuli to control cellular events that impact membrane expansion and composition.
Although recent studies have focused on their role in the central nervous system, little is known about
CREB3 factors in neuronal differentiation. Here, we analyze the expression of CREB3 family members
using two models: i) NGF-induced PC12 cell differentiation and ii) differentiation of embryonic rat
hippocampal neurons. The results show that NGF treatment or developing hippocampal neurons
increases the expression of some proteins necessary for membrane transport (transport factors). In
addition, a significant increase in CREB3L2 mRNA and protein levels is detected in response to NGF,
and expression of both CREB3L1 and CREB3L2 increase in hippocampal neurons (1-7DIV).
Interestingly, CREB3L2-overexpression hampers NGF-induced neurite outgrowth, while its inhibition
enhances it. Consistent with this, CREB3L2-overexpressing PC12 cells show higher expression of
GTPase Rab5 (a negative regulator of PC12 differentiation) than control cells. In contrast, in
hippocampal neurons, CREB3L1 expression is higher than CREB3L2, and overexpression of a
CREB3L1 dominant negative construct reduces axonal growth and increases Golgi fragmentation,
compared to controls. Taken together, our findings strongly suggest that CREB3 factors are involved in
neuronal differentiation by modulating the adaptation of the secretory pathway.
Financing: PICT 2019-1625, BID from the Ministry of Science and Technology of Argentina and SECyT-UNC (2018–2021) from Universidad
Nacional de Córdoba
