Receptor Tyrosine Kinases and Phosphatases in Neuronal Wiring: Insights From Drosophila.

Tyrosine phosphorylation is at the crossroads of many signaling pathways. Brain wiring is not an exception, and several receptor tyrosine kinases (RTKs) and tyrosine receptor phosphates (RPTPs) have been involved in this process. Considerable work has been done on RTKs, and for many of them, detailed molecular mechanisms and functions in several systems have been characterized. In contrast, RPTPs have been studied considerably less and little is known about their ligands and substrates. In both families, we find redundancy between different members to accomplish particular wiring patterns. Strikingly, some RTKs and RPTPs have lost their catalytic activity during evolution, but not their importance in biological processes. In this regard, we have to keep in mind that these proteins have multiple domains and some of their functions are independent of tyrosine phosphorylation/dephosphorylation. Since RTKs and RPTPs are enzymes involved not only in early stages of axon and dendrite pathfinding but also in synapse formation and physiology, they have a potential as drug targets. Drosophila has been a key model organism in the search of a better understanding of brain wiring, and its sophisticated toolbox is very suitable for studying the function of genes with pleiotropic functions such as RTKs and RPTPs, from wiring to synaptic formation and function. In these review, we mainly cover findings from this model organism and complement them with discoveries in vertebrate systems.