RESUMO
In neuronal development, dynamic rearrangement of actin promotes axonal growth cone extension, and spatiotemporal translation of local mRNAs in response to guidance cues directs axonal growth cone steering, where cofilin plays a critical role. While regulation of cofilin activity is well studied, regulatory mechanism for cofilin mRNA translation in neurons is unknown. In eukaryotic cells, proteins can be synthesized by cap-dependent or cap-independent mechanism via internal ribosome entry site (IRES)-mediated translation. IRES-mediated translation has been reported in various pathophysiological conditions, but its role in normal physiological environment is poorly understood. Here, we report that 5'UTR of cofilin mRNA contains an IRES element, and cofilin is predominantly translated by IRES-mediated mechanism in neurons. Furthermore, we show that IRES-mediated translation of cofilin is required for both axon extension and axonal growth cone steering. Our results provide new insights into the function of IRES-mediated translation in neuronal development.
Assuntos
Axônios/fisiologia , Cofilina 1/genética , Cones de Crescimento/fisiologia , Sítios Internos de Entrada Ribossomal/genética , Neurogênese/genética , Regiões 5' não Traduzidas/genética , Animais , Encéfalo/embriologia , Sistemas CRISPR-Cas , Linhagem Celular , Proliferação de Células/genética , Cofilina 1/metabolismo , Camundongos , Biossíntese de Proteínas/genética , RNA Mensageiro/genéticaRESUMO
Local translation of synaptic mRNAs is an important process related to key aspects of central nervous system development and physiology, including dendritogenesis, axonal growth cone morphology and guidance and synaptic plasticity. Accordingly, local translation is compromised in several intellectual disabilities, including Fragile X syndrome, tuberous sclerosis and Down syndrome. Down Syndrome Cell Adhesion Molecule (DSCAM) is a gene with ascribed functions in neuronal wiring that belongs to the Down Syndrome Critical Region (DSCR) of chromosome 21. In this review, we discuss the evidence for local translation of the DSCAM mRNA in dendrites and axonal growth cones of mouse hippocampal neurons, as well as the possible functions of the locally translated DSCAM protein.
Assuntos
Moléculas de Adesão Celular/metabolismo , Dendritos/metabolismo , Síndrome de Down/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Animais , Cones de Crescimento/metabolismo , Humanos , Camundongos , Biossíntese de Proteínas/fisiologiaRESUMO
Developmental changes in the expression and localization of drebrin has been mainly analyzed in chick embryo and young rat by various anti-drebrin polyclonal and monoclonal antibodies. Immunoblot analysis demonstrated that the adult drebrin isoform (drebrin A) is restricted to neural tissues, while the embryonic drebrin isoforms (drebrin E1 and E2 in chicken and drebrin E in mammals) are found in a wide variety of tissues. In the developing brain, drebrin E (including chicken drebrin E2) is expressed in newly generated neurons. During neuronal migration, drebrin E is distributed ubiquitously within the neurons. Once drebrin A is expressed in the developing neuron, drebrin E is no longer present within the cell soma and accumulates in the growth cone of growing processes, resulting in the cessation of neuronal migration. The limited subcellular localization of drebrin A, which is possibly regulated by a drebrin A-specific mechanism, is likely to affect the localization of drebrin E. In the adult brain, drebrin is mainly localized in dendritic spines, but in some nuclei, drebrin can be detected in neuronal somata as well as dendritic spines. The fact that the developmental changes in drebrin expression highly correlate in time with the sensitive period of visual cortical plasticity in kittens suggests that synaptic plasticity depends on drebrin.
Assuntos
Plasticidade Neuronal , Neurônios/metabolismo , Neuropeptídeos/isolamento & purificação , Córtex Visual/diagnóstico por imagem , Animais , Gatos , Embrião de Galinha , Galinhas/metabolismo , Espinhas Dendríticas/química , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/ultraestrutura , Microscopia , Neurônios/química , Neurônios/ultraestrutura , Neuropeptídeos/biossíntese , Neuropeptídeos/metabolismo , Ratos , Córtex Visual/química , Córtex Visual/metabolismoRESUMO
@#The injury of peripheral nerve is generally accompanied with active regeneration responses. This paper is to summarize the molecular mechanism to promote the nerve regeneration, including various reactions of the neuronal body, nerve fiber, and regulatory molecules in the microenvironment, such as transcription factors, inflammatory mediators, nerve growth factors, etc., aiming to investigate the possible mechanism in the nerve regeneration after injury.
RESUMO
Objective To identify the cellular distribution of a my elin-associated protein (Nogo-A) in the central nervous system (CNS) of mice a nd explore its possible inhibition on the CNS axon regeneration after spinal cor d injury. Methods Brain, spinal cord, peripheral tissues and w eight-dropping injuried spinal cord from the adult C57BL/6 mice were studied. N ogo-A protein expression was localized immunohistochemically. Chick E12DRG neur ons were cultured and growth cone collapse assessed. Results N ogo-A protein expression detected was mainly in the oligodendrocyte cell body a nd the myelinated axons surrounded by cell processes rather than in the peripher al tissues. After spinal cord injury, Nogo-A was up-regulated at a moderate de gree in the area around the lesion. Chick E12 DRG growth cone collapse rate was as high as 70%, significantly higher than that in the blank control and vector control groups with a significant difference ( P
