ROLE OF PHOSPHATASES IN OLFACTORY SIGNALING IN MITRAL CELLS**
Mitral cells are the output cell from the olfactory bulb to other brain regions, and the voltage-gated potassium channel, Kv1.3, carries the majority of the outward current in these neurons. Kv1.3 activity is regulated by tyrosine phosphorylation. Very little is known about the counter mechanism of dephosphorylation by phosphatases in the mitral cells. The goal of this study is to determine the expression of phosphatases in mitral cells of wildtype and Kv1.3-null mice, and to relate protein expression changes to the previously observed electrophysiology and phosphorylation changes in these mice. Since the insulin receptor kinase regulates the phosphorylation state of Kv1.3 in native mouse mitral cells, candidate phosphatases known to be involved in insulin signaling pathways in other cells were screened for their expression levels in the olfactory bulb. Three candidates, SH2 domain containing phosphatase-2 (SHP-2), protein tyrosine phosphatase 1B (PTP-1B), and MAP kinase phosphatase-1 (MKP-1), are expressed throughout the olfactory bulb, including in the mitral cell layer. The expression of all three phosphatases is reduced in Kv1.3-null mice when compared to wildtype mice. Deletion of Kv1.3 causes the mitral cells to have increased total tyrosine phosphorylation levels. Therefore, the decreases in SHP-2, PTP-1B, and MKP-1 expression in the Kv1.3-null mice align with the increased total tyrosine phosphorylation levels observed previously. The increased phosphorylation generally suppresses the current in Kv family members, which may explain the altered biophysics observed in the transgenic mice. Future work will focus on understanding the functional role of SHP-2, PTP-1B, and MKP-1 in modulating the neural activity and intracellular signaling cascades in the mitral cell both in vitro and in vivo.
NIH NIDCD AREA Grant, UWG COSM Research Initiative Award, UWG Faculty Research Grant
Johnson, Melissa Cavallin; Cano*, Carlos; Loberbaum-Fears*, Kim; Wharton*, Adam; and Parks*, Thomas
"ROLE OF PHOSPHATASES IN OLFACTORY SIGNALING IN MITRAL CELLS**,"
Georgia Journal of Science, Vol. 76, No. 1, Article 103.
Available at: https://digitalcommons.gaacademy.org/gjs/vol76/iss1/103