Expression of the neurotrophin receptor trkB is regulated by the cAMP/CREB pathway in neurons.
trkB as receptor for neurotrophins brain-derived neurotrophic factor (BDNF)/neurotrophin (NT)-4/5 plays a crucial role during development, maintenance of the adult brain, and its adaptation to injury or pathological conditions. In spite of this, very little is known about the mechanisms that regulate its expression. Here, we show that forskolin (Fk) rapidly stimulates the expression of both the full-length and truncated trkB isoforms in primary cultures of cortical neurons. Gel shift assays and transient transfection experiments demonstrate that this activation occurs via a protein kinase A (PKA)/cyclic AMP-responsive element-binding protein (CREB)-dependent mechanism. Activated CREB binds to the second cyclic AMP (cAMP)-responsive element (CRE) of the two CRE sites located within the P2 promoter of the trkB gene, which is able to confer cAMP responsiveness to a heterologous promoter. Our results illustrate that the trkB gene is a target for CREB regulation and explain the increase of trkB expression produced in different adaptative responses of the nervous system where CREB is participating.
Deogracias
Rubén
R
Instituto de Investigaciones Biomédicas "Alberto Sols" CSIC-UAM, 28029 Madrid, Spain.
Espliguero
Gemma
G
Iglesias
Teresa
T
Rodríguez-Peña
Angeles
A
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D005576:Colforsin; D020813:Receptor, trkB