Novel function of PTP69D in giant fiber synapse formation

PTP69D is a receptor protein tyrosine phosphatase RPTP with two intracellular catalytic
domains Cat1 and Cat2, which has been shown to play a role in axon outgrowth and guidance of
embryonic motoneurons as well as targeting of photoreceptor neurons in the visual system of
Drosophila melanogaster. Here, we characterized the developmental role of PTP69D in the giant
fiber GF neurons; two interneurons in the central nervous system CNS that control the escape
response of the fly. In addition to guidance and targeting functions, our studies reveal an
additional role for PTP69D in synaptic terminal growth in the CNS. We found that inhibition of
phosphatase activity in catalytic domain Cat1 proximal to the transmembrane domain did not
affect axon guidance or targeting but resulted in stunted terminal growth of the GFs. Cell
autonomous rescue and knockdown experiments demonstrated a function for PTP69D in the
GFs, but not its postsynaptic target neurons. In addition, complementation studies and structurefunction
analyses revealed that for GF terminal growth Cat1 function of PTP69D requires the
Immunoglobulin and the Cat2 domain, but not the Fibronectin III and the Membrane Proximal
Region domains. In contrast, the Fibronectin III, but not the Immunoglobulin domains, were
previously shown to be essential for axon targeting of photoreceptor neurons. Thus, our studies
uncover a novel role for PTP69D in synaptic terminal growth in the CNS that is mechanistically
distinct from its function during earlier developmental process.