Regulation of the neuron-specific exon of clathrin light chain B.
Clathrin light chain B (LCB) is a major component of clathrin coated vesicles, which are structures involved in intracellular transport. A neuron-specific isoform of LCB is generated by incorporation of a single exon (EN) using an alternative splicing mechanism that reflects the special demands of neurons, such as axonal transport and synaptic neurotransmission. Here, we demonstrate that this neuron-specific exon is developmentally regulated and is excluded in non-neuronal cells because its 5' and 3' splice sites deviate from the mammalian consensus sequences. A gel retardation assay indicated the presence of a developmentally regulated factor in brain that binds to the neuronal exon. In addition, EN usage is repressed by increasing the concentration of htra2-beta1, a splice factor whose isoform expression is influenced by neuronal activity. We propose that a brain-specific factor is involved in EN recognition during development and adulthood. In addition, ubiquitously expressed splicing factors such as htra2-beta1 are involved in regulating EN expression in the adult brain.
Stamm
S
S
Max-Planck-Institute of Neurobiology, Am Klopferspitz 18a, D-82152 Martinsried, Germany. stamm@pop1.biochem.mpg.de
Casper
D
D
Hanson
V
V
Helfman
D M
DM
D000367:Age Factors; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001370:Axonal Transport / Q000235:genetics; D002966:Clathrin / Q000235:genetics*; D018699:Coated Vesicles / Q000737:chemistry; D005091:Exons / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008322:Mammals; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D015345:Oligonucleotide Probes; D012313:RNA / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis; D014158:Transcription, Genetic / Q000502:physiology; D014162:Transfection
D002966:Clathrin; D015345:Oligonucleotide Probes; D016601:RNA-Binding Proteins; D012313:RNA