The insect homologue of the amyloid precursor protein interacts with the heterotrimeric G protein Go alpha in an identified population of migratory neurons.
The amyloid precursor protein (APP) is the source of Abeta fragments implicated in the formation of senile plaques in Alzheimer's disease (AD). APP-related proteins are also expressed at high levels in the embryonic nervous system and may serve a variety of developmental functions, including the regulation of neuronal migration. To investigate this issue, we have cloned an orthologue of APP (msAPPL) from the moth, Manduca sexta, a preparation that permits in vivo manipulations of an identified set of migratory neurons (EP cells) within the developing enteric nervous system. Previously, we found that EP cell migration is regulated by the heterotrimeric G protein Goalpha: when activated by unknown receptors, Goalpha induces the onset of Ca2+ spiking in these neurons, which in turn down-regulates neuronal motility. We have now shown that msAPPL is first expressed by the EP cells shortly before the onset of migration and that this protein undergoes a sequence of trafficking, processing, and glycosylation events that correspond to discrete phases of neuronal migration and differentiation. We also show that msAPPL interacts with Goalpha in the EP cells, suggesting that msAPPL may serve as a novel G-protein-coupled receptor capable of modulating specific aspects of migration via Goalpha-dependent signal transduction.
Swanson
T L
TL
Department of Cell & Developmental Biology, L-215, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Knittel
L M
LM
Coate
T M
TM
Farley
S M
SM
Snyder
M A
MA
Copenhaver
P F
PF
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000737:chemistry / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018402:Manduca / Q000196:embryology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009474:Neurons / Q000145:classification / Q000166:cytology* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D019206:GTP-Binding Protein alpha Subunits, Gi-Go