Amyloid Precursor Protein family as unconventional Go-coupled receptors and the control of neuronal motility.
Cleavage of the Amyloid Precursor Protein (APP) generates amyloid peptides that accumulate in Alzheimer Disease (AD), but APP is also upregulated by developing and injured neurons, suggesting that it regulates neuronal motility. APP can also function as a G protein-coupled receptor that signals via the heterotrimeric G protein Gαo, but evidence for APP-Gαo signalingin vivohas been lacking. UsingManducaas a model system, we showed that insect APP (APPL) regulates neuronal migration in a Gαo-dependent manner. Recently, we also demonstrated thatManducaContactin (expressed by glial cells) induces APPL-Gαo retraction responses in migratory neurons, consistent with evidence that mammalian Contactins also interact with APP family members. Preliminary studies using cultured hippocampal neurons suggest that APP-Gαo signaling can similarly regulate growth cone motility. Whether Contactins (or other APP ligands) induce this response within the developing nervous system, and how this pathway is disrupted in AD, remains to be explored.
Department of Cell, Developmental and Cancer Biology L-215, Oregon Health & Sciences University , Portland, OR, USA.
Jenna M
JM
Ramaker
Department of Cell, Developmental and Cancer Biology L-215, Oregon Health & Sciences University , Portland, OR, USA.
Philip F
PF
Copenhaver
APP; APPL; G protein; Gαo; Manduca; growth cone; hippocampal neuron; neuronal migration