882B Poster - 14. Neural circuits and behavior
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Emily Hendricks; Taylor Delaney; Faith Liebl

Affiliation: Southern Illinois University Edwardsville

Keywords:
e. synaptic function and organization; f. neuromuscular junction

Chromodomain helicase binding domain (CHD) proteins, including CHD7 and CHD8, remodel chromatin to alter transcriptional programs. Both proteins are important for proper neural development as heterozygous mutations in Chd7 and Chd8 are causative for CHARGE syndrome and correlated with autism spectrum disorders, respectively. Their roles in mature neurons are poorly understood despite influencing the expression of genes required for cell adhesion, neurotransmission, and synaptic plasticity. The Drosophila homolog of CHD7 and CHD8, Kismet (Kis), promotes neurotransmission, endocytosis, and larval movement, and restricts synaptic levels of cell adhesion molecules. Endocytosis is essential in neurons for replenishing synaptic vesicles, maintaining protein localization, and preserving the size and composition of the presynaptic membrane. Endocytosis can occur via clathrin-mediated endocytosis (CME), which is coupled with neural activity and is the most prevalent form of synaptic endocytosis, and activity-dependent bulk endocytosis, which occurs during periods of intense stimulation. We assessed transcripts important for endocytosis in kis mutant central nervous systems. AP2α, dap160/intersectin, and endophilin B (endoB), required for CME, show differential expression in kis mutants. Rab11, akt, PI3K92E, and sgg/GSK3β, required for ADBE, exhibit reduced transcripts levels. Finally, syndapin transcripts, required for both CME and ADBE, were reduced while several other transcripts were unaffected by mutations in kis. We were able to restore endoB, PI3K92E, rab11, and sgg transcripts in kis mutants by expressing kis in either neurons or postsynaptic muscle. These data indicate that Kis contributes to both CME and ADBE. We further tested this hypothesis by pharmacologically inhibiting either CME or ADBE in kis mutants and examined endocytosis both electrophysiologically and functionally. Collectively, our data indicate that Kis promotes both CME and ADBE by promoting transcription of several endocytic genes.