Developmental expression of the SRF co-activator MAL in brain: role in regulating dendritic morphology.
The dynamic changes in dendritic morphology displayed by developing and mature neurons have stimulated interest in deciphering the signaling pathways involved. Recent studies have identified megakaryocytic acute leukemia (MAL), a serum response factor (SRF) co-activator, as a key component of a signaling pathway linking changes in the actin cytoskeleton to SRF-mediated transcription. To help define the role of this pathway in regulating dendritic morphology, we have characterized the pattern of MAL expression in the developing and adult brain, and have examined its role in regulating dendritic morphology in cultured cortical neurons. In histological studies of mouse brain, we found prominent expression of MAL in neurons in adult hippocampus and cerebral cortex. MAL immunostaining revealed localization of this protein in neuronal cell bodies and apical dendrites. During development, an increase in MAL expression occurs during the second post-natal week. Expression of dominant negative MAL constructs or MAL siRNA in cortical neurons grown in primary culture reduces the number of dendritic processes and decreases the basal level of SRF-mediated transcription. Taken together, these findings indicate that the MAL-SRF signaling pathway plays a key role in regulating dendritic morphology.
Shiota
Jun
J
Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama City, Japan.
Ishikawa
Mitsuru
M
Sakagami
Hiroyuki
H
Tsuda
Masaaki
M
Baraban
Jay M
JM
Tabuchi
Akiko
A
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure*; D002540:Cerebral Cortex / Q000166:cytology; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure*; D004622:Embryo, Mammalian / Q000378:metabolism; D005799:Genes, Dominant; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D017434:Protein Structure, Tertiary / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D014018:Tissue Distribution; D015534:Trans-Activators
D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C511173:Mrtfa protein, mouse; D015534:Trans-Activators