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 PTPalpha, leukocyte common antigen-related, or PTPdelta. 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+ 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+ 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.
