Analysis of three μ1-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 μ1-adaptin genes, encoding μ1A, μ1B, and the novel isoform μ1C, which is not found in mammals. μ1C shows 80% sequence identity with μ1A and μ1B. The μ1C expression pattern largely overlaps with that of μ1A, while μ1B is expressed in epithelial cells. By knocking-down the synthesis of μ1A, μ1B and μ1C with antisense morpholino techniques we demonstrate that each of these μ1 adaptins is essential for zebrafish development, with μ1A and μ1C being involved in central nervous system development and μ1B in kidney, gut and liver 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 cannot be fulfilled by one of the other isoforms. Each of the μ1 adaptins appears to mediate specific molecular mechanisms essential for early developmental processes, which depends on specific intracellular vesicular protein sorting pathways.