DeBakey Awards

Ronald L. Davis, Ph.D.

Molecular & Cellular Biology

1998 Recipient

Integrins in the central nervous system: thanks for the memories

Genetic screens in Drosophila have uncovered several genes that are required for normal learning and memory. Previous research has shown that genes encoding components of the cyclic AMP signaling system are important for memory formation. These include dunce ( cAMP phosphodiesterase), rutabaga (adenylyl cyclase), DCO (protein kinase A), and CREB (cyclic AMP binding protein). The newest molecular players in memory to be found from such screens are cell adhesion molecules of the integrin family. These molecules have been well studied for their roles in cancer and blood cell biology and are known to dynamically mediate cell adhesion and signal transduction.

Dr. Davis’ laboratory discovered the Volado gene which is required for normal learning and memory. The Volado locus encodes two forms of a novel α-integrin. The gene is expressed preferentially in brain regions that are known to mediate olfactory learning in insects, and the Volado proteins are compartmentalized primarily to the axons and dendrites of neurons in this region. Volado mutants display impaired olfactory memory within 3 minutes after training, indicating an essential role for the integrin in short-term processes. Conditional expression of a Volado transgene during adulthood rescues the memory impairment; this rescue is reversible, fading in time along with expression of the transgene. By controlling expression of the transgene before or after training, Dr. Davis demonstrated that integrins are not required solely for retrieval of memories. Rather, integrins mediate the formation and the stability of new memories. It is hypothesized that these molecules participate in structural rearrangements of synapses important for learning through altered affinity for molecules in the synaptic cleft, or for ligands displayed by the synaptic partner neuron.

Dr. Davis’s nomination was based on the following publications:

Skoulakis EM, Davis RL. Olfactory learning deficits in mutants for leonardo, a Drosophila gene encoding a 14-3-3 protein. Neuron. 1996 Nov;17(5):931-44.

Meller VH, Wu KH, Roman G, Kuroda MI, Davis RL. roX1 RNA paints the X chromosome of male Drosophila and is regulated by the dosage compensation system. Cell. 1997 Feb 21;88(4):445-57.

Grotewiel MS, Beck CD, Wu KH, Zhu XR, Davis RL. Integrin-mediated short-term memory in Drosophila. Nature. 1998 Jan 29;391(6666):455-60.