The fragile X-related gene affects the crawling behavior of Drosophila larvae by regulating the mRNA level of the DEG/ENaC protein pickpocket1.

Background: Fragile X syndrome is caused by loss-of-function mutations in the fragile X mental retardation 1 (FMR1) gene. How FMR1 affects the function of the central and peripheral nervous systems is still unclear. FMR1 is an RNA binding protein that associates with a small percentage of total mRNAs in vivo.

The organization of engaged and quiescent translocons in the endoplasmic reticulum of mammalian cells.

Protein translocons of the mammalian endoplasmic reticulum are composed of numerous functional components whose organization during different stages of the transport cycle in vivo remains poorly understood. We have developed generally applicable methods based on fluorescence resonance energy transfer (FRET) to probe the relative proximities of endogenously expressed translocon components in cells. Examination of substrate-engaged translocons revealed oligomeric assemblies of the Sec61 complex that were associated to varying degrees with other essential components including the signal recognition particle receptor TRAM and the TRAP complex.

Control of dendritic development by the Drosophila fragile X-related gene involves the small GTPase Rac1.

Fragile X syndrome is caused by loss-of-function mutations in the fragile X mental retardation 1 gene. How these mutations affect neuronal development and function remains largely elusive. We generated specific point mutations or small deletions in the Drosophila fragile X-related (Fmr1) gene and examined the roles of Fmr1 in dendritic development of dendritic arborization (DA) neurons in Drosophila larvae.

Genetic control of dendritic morphogenesis in Drosophila.

How the dendritic branching patterns of different neurons are specified is a fascinating question in developmental neurobiology. This question can now be addressed in detail in Drosophila, owing to technological advances that allow in vivo labeling of the dendrites of identifiable neurons. Recent genetic analyses in flies have uncovered several molecules, including transcription factors, cytoskeleton-associated proteins and membrane receptor-like molecules, that provide a glimpse into the complex regulatory network that controls dendritic morphogenesis.

Substrate-specific function of the translocon-associated protein complex during translocation across the ER membrane.

Although the transport of model proteins across the mammalian ER can be reconstituted with purified Sec61p complex, TRAM, and signal recognition particle receptor, some substrates, such as the prion protein (PrP), are inefficiently or improperly translocated using only these components. Here, we purify a factor needed for proper translocation of PrP and identify it as the translocon-associated protein (TRAP) complex. Surprisingly, TRAP also stimulates vectorial transport of many, but not all, other substrates in a manner influenced by their signal sequences.