Receptor-Like Tyrosine Phosphatase PTP10D Is Required for Long-Term Memory inDrosophila

Abstract

Tyrosine phosphorylation mediates multiple signal transduction pathways that play key roles in developmental processes and behavioral plasticity. The level of tyrosine phosphorylation is regulated by protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Extensive studies have investigated the roles of tyrosine kinases in memory formation. However, there were few studies on PTPs. To date, learning has been shown to be defective only for mouse knock-outs of PTP␣, leukocyte common antigen-related, or PTP␦. A major limitation of these studies arises from their inability to distinguish an acute (biochemical) impairment of memory formation from a more chronic abnormality in neurodevelopment. From a behavioral screen for defective long-term memory, we found chi mutants to disrupt expression of the PTP10D protein tyrosine phosphatase gene. We show that chi mutants are normal for learning, early memory, and anesthesia-resistant memory, whereas long-term memory specifically is abolished. Significantly, induction of a heat shock-PTP10D ϩ transgene before training fully rescues the memory defect of chi mutants, thereby demonstrating an acute role for PTP10D in behavioral plasticity. We show that PTP10D is widely expressed in the embryonic CNS and in the adult brain. Transgenic expression of upstream activating sequence-PTP10D ϩ in mushroom bodies is sufficient to rescue the memory defect of chi mutants. Our data clearly demonstrate that signaling through PTP10D in mushroom bodies is critical for the formation of long-term memory.

Nucleotide diversity inflation as a genome-wide response to experimental lifespan extension in Drosophila melanogaster

“…One protein receptor gene ( Ptp10D ) belonging to the protein-tyrosine phosphatase family was under significant positive selection in the comparison between selection and control groups (Ka/Ks = 9, McDonald-Kreitman test p  = 0.0217). Ptp10D is responsible for central nervous system development [36], axon guidance [37], and long-term memory [38]. Another gene with Ka/Ks = 4 (but MKT p  > 0.05) was Ank2 , involved in axon extension [39], neuron cellular homeostasis [39], sensory perception of pain [40] and short-term memory [41].…”

Divergent Functions Through Alternative Splicing: The Drosophila CRMP Gene in Pyrimidine Metabolism, Brain, and Behavior

“…In contrast with STM and MTM, LTM measured through the spaced training paradigm used in these studies requires acute protein synthesis under control of the CREB transcription factor (Tully et al 1994;Yin et al 1995;Qian et al 2007;Wu et al 2007). Given the reduced performance observed at earlier time points, we cannot distinguish whether the LTM phenotype is due to an active requirement for CRMP function during memory consolidation or rather if the LTM defect is a consequence of reduced acquisition.…”

R3 receptor tyrosine phosphatases: Conserved regulators of receptor tyrosine kinase signaling and tubular organ development

“…The viability of Ptp4E and Ptp10D mutants is due to redundancy between these closely related R3 RPTPs, because Ptp4E Ptp10D double mutants die at the end of embryogenesis(Jeon et al, 2008a, b; Jeon and Zinn, 2009b). The only single mutant phenotype that has been reported for an R3 RPTP is a defect in long-term memory formation in Ptp10D mutant adults (Qian et al, 2007). …”