Analysis of three μ-AP1 subunits during zebrafish development

Background: The family of AP-1 complexes mediates protein sorting in the late secretory pathway and it is essential for the development of mammals. The ubiquitously expressed AP-1A complex consists of four adaptins γ1, β1, μ1A and σ1A. AP-1A mediates protein transport between the trans-Golgi network and early endosomes The polarized epithelia AP-1B complex contains the μ1B-adaptin. AP-1B mediates specific transport of proteins from basolateral recycling endosomes to the basolateral plasma membrane of polarized epithelial cells. Results: Analysis of the zebrafish genome revealed the existence of three 1-adaptin genes, encoding 1A, 1B and the novel isoform μ1C, which is not found in mammals. μ1C shows 80% sequence identity with 1A and 1B. The 1C expression pattern largely overlaps with that of 1A, while 1B is expressed in epithelial cells. By knocking-down the synthesis of 1A, 1B and 1C with antisense morpholino techniques we demonstrate that each of these 1 adaptins is essential for zebrafish development, with 1A and 1C being involved in central nervous system development and 1B in kidney formation. Conclusions: Zebrafish is unique in expressing three AP-1 complexes: AP-1A, AP-1B and AP-1C. Our results demonstrate that they are not redundant and that each of them has specific functions, which can not be fulfilled by one of the other isoforms. Each of the 1 adaptins appears to mediate specific molecular mechanisms essential for early developmental processes, which depend on specific intracellular vesicular protein sorting pathways.