RT Journal Article
SR Electronic
T1 <em>Drosophila rugose</em> Is a Functional Homolog of Mammalian <em>Neurobeachin</em> and Affects Synaptic Architecture, Brain Morphology, and Associative Learning
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 15193
OP 15204
DO 10.1523/JNEUROSCI.6424-11.2012
VO 32
IS 43
A1 Karolien Volders
A1 Sabrina Scholz
A1 Jan R. Slabbaert
A1 Anja C. Nagel
A1 Patrik Verstreken
A1 John W. M. Creemers
A1 Patrick Callaerts
A1 Martin Schwärzel
YR 2012
UL http://www.jneurosci.org/content/32/43/15193.abstract
AB Neurobeachin (Nbea) is implicated in vesicle trafficking in the regulatory secretory pathway, but details on its molecular function are currently unknown. We have used Drosophila melanogaster mutants for rugose (rg), the Drosophila homolog of Nbea, to further elucidate the function of this multidomain protein. Rg is expressed in a granular pattern reminiscent of the Golgi network in neuronal cell bodies and colocalizes with transgenic Nbea, suggesting a function in secretory regulation. In contrast to Nbea−/− mice, rg null mutants are viable and fertile and exhibit aberrant associative odor learning, changes in gross brain morphology, and synaptic architecture as determined at the larval neuromuscular junction. At the same time, basal synaptic transmission is essentially unaffected, suggesting that structural and functional aspects are separable. Rg phenotypes can be rescued by a Drosophila rg+ transgene, whereas a mouse Nbea transgene rescues aversive odor learning and synaptic architecture; it fails to rescue brain morphology and appetitive odor learning. This dissociation between the functional redundancy of either the mouse or the fly transgene suggests that their complex composition of numerous functional and highly conserved domains support independent functions. We propose that the detailed compendium of phenotypes exhibited by the Drosophila rg null mutant provided here will serve as a test bed for dissecting the different functional domains of BEACH (for beige and human Chediak–Higashi syndrome) proteins, such as Rugose, mouse Nbea, or Nbea orthologs in other species, such as human.