Zebrafish orthologue of mental retardation protein IL1RAPL1 regulates presynaptic differentiation.
IL1-receptor accessory protein-like 1 (IL1RAPL1), a member of interleukin-1/toll receptor (TIR) family, is responsible for a nonsyndromic form of mental retardation (MR). The zebrafish orthologue of mammalian IL1RAPL1, designated as Il1rapl1b, was expressed widely in the brain and in the olfactory placode. We employed an olfactory sensory neuron-specific gene manipulation system in combination with in vivo imaging of transparent zebrafish embryos to examine the functional role of Il1rapl1b in synaptic vesicle accumulation and subsequent morphological remodeling of axon terminals, the characteristic features of presynaptic differentiation of zebrafish olfactory sensory neurons during synapse formation. Antisense morpholino oligonucleotide against il1rapl1b suppressed both the synaptic vesicle accumulation and axon terminal remodeling. Consistently, the overexpression of Il1rapl1b stimulated synaptic vesicle accumulation. Swapping the carboxyl-terminal domain of Il1rapl1b with that of mouse IL-1 receptor accessory protein abolished the stimulatory effect. On the other hand, a substitution mutation in the TIR domain suppressed the morphological remodeling of axon terminals. Thus, the regulation of synaptic vesicle accumulation and subsequent morphological remodeling by Il1rapl1b appeared to be mediated by distinct domains. These results suggest that Il1rapl1b plays an important role in presynaptic differentiation during synapse formation.
Yoshida
Tomoyuki
T
Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Mishina
Masayoshi
M
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D003001:Cloning, Molecular / Q000379:methods; D004625:Embryo, Nonmammalian; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics / Q000502:physiology*; D008845:Microinjections / Q000379:methods; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000166:cytology* / Q000502:physiology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
D019922:GAP-43 Protein; D053577:Interleukin-1 Receptor Accessory Protein; D018832:Molecular Chaperones; D020319:Oligodeoxyribonucleotides, Antisense; D029961:Zebrafish Proteins; C485184:enhanced green fluorescent protein; C110856:proteasome maturation protein; D049452:Green Fluorescent Proteins