GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:18354025

From GONUTS
Jump to: navigation, search
Citation

Reeve, SP, Lin, X, Sahin, BH, Jiang, F, Yao, A, Liu, Z, Zhi, H, Broadie, K, Li, W, Giangrande, A, Hassan, BA and Zhang, YQ (2008) Mutational analysis establishes a critical role for the N terminus of fragile X mental retardation protein FMRP. J. Neurosci. 28:3221-6

Abstract

Fragile X syndrome is the most common form of heritable mental retardation caused by the loss of function of the fragile X mental retardation protein FMRP. FMRP is a multidomain, RNA-binding protein involved in RNA transport and/or translational regulation. However, the binding specificity between FMRP and its various partners including interacting proteins and mRNA targets is essentially unknown. Previous work demonstrated that dFMRP, the Drosophila homolog of human FMRP, is structurally and functionally conserved with its mammalian counterparts. Here, we perform a forward genetic screen and isolate 26 missense mutations at 13 amino acid residues in the dFMRP coding dfmr1. Interestingly, all missense mutations identified affect highly conserved residues in the N terminal of dFMRP. Loss- and gain-of-function analyses reveal altered axonal and synaptic elaborations in mutants. Yeast two-hybrid assays and in vivo analyses of interaction with CYFIP (cytoplasmic FMR1 interacting protein) in the nervous system demonstrate that some of the mutations disrupt specific protein-protein interactions. Thus, our mutational analyses establish that the N terminus of FMRP is critical for its neuronal function.

Links

PubMed Online version:10.1523/JNEUROSCI.5528-07.2008

Keywords

Amino Acid Sequence; Animals; Animals, Genetically Modified; Base Sequence; Central Nervous System/metabolism; Conserved Sequence; DNA Mutational Analysis/methods; Drosophila; Drosophila Proteins/genetics; Fragile X Mental Retardation Protein/chemistry; Fragile X Mental Retardation Protein/genetics; Gene Expression Regulation; Molecular Sequence Data; Mutation/physiology; Neuromuscular Junction/metabolism; Neurons/metabolism; Peripheral Nerves/cytology; Protein Structure, Tertiary; Two-Hybrid System Techniques

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:FMR1

involved_in

GO:0007528: neuromuscular junction development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:FMR1

involved_in

GO:0048812: neuron projection morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.