The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning

The assembly of neuronal circuits involves the migrations of neurons from their place of birth to their final location in the nervous system, as well as the coordinated growth and patterning of axons and dendrites. In screens for genes required for patterning of the nervous system, we identified the <jats:italic>catp-8/P5A-ATPase</jats:italic> as an important regulator of neural patterning. P5A-ATPases are part of the P-type ATPases, a family of proteins known to serve a conserved function as transporters of ions, lipids and polyamines in unicellular eukaryotes, plants, and humans. While the function of many P-type ATPases is relatively well understood, the function of P5A-ATPases in metazoans remained elusive. We show here, that the <jats:italic>Caenorhabditis elegans</jats:italic> ortholog <jats:italic>catp-8/P5A-ATPase</jats:italic> is required for defined aspects of nervous system development. Specifically, the <jats:italic>catp-8/P5A-ATPase</jats:italic> serves functions in shaping the elaborately sculpted dendritic trees of somatosensory PVD neurons. Moreover, <jats:italic>catp-8/P5A-ATPase</jats:italic> is required for axonal guidance and repulsion at the midline, as well as embryonic and postembryonic neuronal migrations. Interestingly, not all axons at the midline require <jats:italic>catp-8/P5A-ATPase</jats:italic>, although the axons run in the same fascicles and navigate the same space. Similarly, not all neuronal migrations require <jats:italic>catp-8/P5A-ATPase</jats:italic>. A CATP-8/P5A-ATPase reporter is localized to the ER in most, if not all, tissues and <jats:italic>catp-8/P5A-ATPase</jats:italic> can function both cell-autonomously and non-autonomously to regulate neuronal development. Genetic analyses establish that <jats:italic>catp-8/P5A-ATPase</jats:italic> can function in multiple pathways, including the Menorin pathway, previously shown to control dendritic patterning in PVD, and Wnt signaling, which functions to control neuronal migrations. Lastly, we show that <jats:italic>catp-8/P5A-ATPase</jats:italic> is required for localizing select transmembrane proteins necessary for dendrite morphogenesis. Collectively, our studies suggest that <jats:italic>catp-8/P5A-ATPase</jats:italic> serves diverse, yet specific, roles in different genetic pathways and may be involved in the regulation or localization of transmembrane and secreted proteins to specific subcellular compartments.