Lee, LaTasha Hoskins

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.

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 motorneurons, 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 structure-function analyses revealed that for GF terminal growth, Cat1 function of PTP69D requires the immunoglobulin and the Cat2 domain but not the fibronectin type III repeats nor the membrane proximal region. In contrast, the fibronectin type III repeats, 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 processes.