The Drosophila cell adhesion molecule Klingon is required for long-term memory formation and is regulated by Notch

Abstract

The ruslan (rus) mutant was previously identified in a behavioral screen for mutants defective in long-lasting memory, which consists of two consolidated memory types, anesthesia-resistant memory, and protein synthesis-dependent long-term memory (LTM). We demonstrate here that rus is a new allele of klingon (klg), which encodes a homophilic cell adhesion molecule. Klg is acutely required for LTM but not anesthesia-resistant memory formation, and Klg expression increases upon LTM induction. LTM formation also requires activity of the Notch cell-surface receptor. Although defects in Notch have been implicated in memory loss because of Alzheimer's disease, downstream signaling linking Notch to memory have not been determined. Strikingly, we found that Notch activity increases upon LTM induction and regulates Klg expression. Furthermore, Notch-induced enhancement of LTM is disrupted by a klg mutation. We propose that Klg is a downstream effector of Notch signaling that links Notch activity to memory. memory consolidation ͉ ruslan ͉ Alzheimer's disease

The Genetics of Alcohol Responses of Invertebrate Model Systems

“…In flies, a number of cell-adhesion molecules have been shown to affect ethanol responses. The Notchregulated cell-adhesion gene klingon is required for normal olfactory memory (Matsuno, Horiuchi, Tully, & Saitoe, 2009) and for ethanol sedation and tolerance (Berger et al, 2008), whereas the neural cell-adhesion molecule FasII is required for normal acute resistance to ethanol as well as for normal olfactory learning (Cheng et al, 2001). Interestingly, FasII protein levels are reduced in the hangover tolerance mutant (Schwenkert et al, 2008), suggesting that the hangover-encoded transcription factor might directly regulate FasII expression and thereby cell adhesion.…”

dEHBP1 regulates Scabrous secretion during Notch mediated lateral inhibition

“…Notch has also been implicated in the control of sleep (Seugnet et al, 2011;Singh et al, 2011). Finally, Notch activity is required for memory formation in Drosophila and mice (Costa et al, 2003;Ge et al, 2004;Matsuno et al, 2009;Presente et al, 2004). Intriguingly, loss of function of sca disrupts the formation of memories for ethanol reward without disrupting apparent features of the corresponding neuronal circuitry (Kaun et al, 2011).…”

DrosophilaNeurexin IV stabilizes neuron-glia interactions at the CNS midline by binding to Wrapper

“…Interestingly, Wrapper appears to be less conserved. Although it is present in all Drosophilidae and the Drosophila genome harbors a Wrapper-related protein, Klingon (Butler et al, 1997;Matsuno et al, 2009), no clear Wrapper orthologs can be identified in mammals. However, there are several GPI-linked Ig-superfamily proteins in the mouse genome whose expression profiles need to be determined.…”