TRPM7 function in zebrafish dopaminergic neurons

Abstract

TRPM7 (Transient Receptor Potential Melastatin-like 7) is an ion channel necessary for the proper development of many cell types. Insight into the precise role of the channel in different cells has been hampered by the lethality of knocking out the gene in model organisms such as the mouse. Here I examine a zebrafish that has a loss-offunction mutation in the gene encoding Trpm7. First, I show that trpm7 is important for the function of developing dopaminergic neurons in the zebrafish. Second, I examine the interaction between trpm7 and the related gene vmat2 in order to develop a cellular mechanism of Trpm7 function in presynaptic dopaminergic neurons. Finally, I investigate the necessity of the kinase and ion channel domains of trpm7 in their ability to promote pigmentation in melanophores as a model cell type. Based on the results from these experiments and observations from other researchers, I form a new hypothesis for Trpm7 function in protein sorting. These studies provide a detailed and novel analysis of the function of an ion channel that is necessary for life. vi

Motility phenotype in a zebrafish vmat2 mutant

“…Jointly, these studies have documented both motor and non-motor symptoms of PD in various assays including assays for strength, gait, olfaction, and sleep [ 15 , 16 ]. The peptide sequences of zebrafish Slc18a2 and human SLC18A2 are 75% identical [ 17 ]. Expression of zebrafish vmat2 overlaps with expression of tyrosine hydroxylase 1 (TH), a molecular marker for DA, throughout the larval zebrafish brain [ 18 ].…”