Spd-2 gene duplication reveals cell-type-specific pericentriolar material regulation

• Published in: Current biology 2023-07, Vol.33 (14), p.3031-3040.e6
• Main Authors: O’Neill, Ryan S., Sodeinde, Afeez K., Welsh, Frances C., Fagerstrom, Carey J., Galletta, Brian J., Rusan, Nasser M.
• Format: Article
• Language: English
• Subjects: cell-type-specific function; centrosome; Drosophila; evolutionary cell biology; gene duplication; meiosis; mitosis; PCM; pericentriolar material; Spd-2
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2023.06.020

Centrosomes are multi-protein organelles that function as microtubule (MT) organizing centers (MTOCs), ensuring spindle formation and chromosome segregation during cell division.1,2,3 Centrosome structure includes core centrioles that recruit pericentriolar material (PCM) that anchors γ-tubulin to nucleate MTs.1,2 In Drosophila melanogaster, PCM organization depends on proper regulation of proteins like Spd-2, which dynamically localizes to centrosomes and is required for PCM, γ-tubulin, and MTOC activity in brain neuroblast (NB) mitosis and male spermatocyte (SC) meiosis.4,5,6,7,8 Some cells have distinct requirements for MTOC activity due to differences in characteristics like cell size9,10 or whether they are mitotic or meiotic.11,12 How centrosome proteins achieve cell-type-specific functional differences is poorly understood. Previous work identified alternative splicing13 and binding partners14 as contributors to cell-type-specific differences in centrosome function. Gene duplication, which can generate paralogs with specialized functions,15,16 is also implicated in centrosome gene evolution,17 including cell-type-specific centrosome genes.18,19 To gain insight into cell-type-specific differences in centrosome protein function and regulation, we investigated a duplication of Spd-2 in Drosophila willistoni, which has Spd-2A (ancestral) and Spd-2B (derived). We find that Spd-2A functions in NB mitosis, whereas Spd-2B functions in SC meiosis. Ectopically expressed Spd-2B accumulates and functions in mitotic NBs, but ectopically expressed Spd-2A failed to accumulate in meiotic SCs, suggesting cell-type-specific differences in translation or protein stability. We mapped this failure to accumulate and function in meiosis to the C-terminal tail domain of Spd-2A, revealing a novel regulatory mechanism that can potentially achieve differences in PCM function across cell types. •Drosophila willistoni harbors a duplication of the centrosome gene Spd-2•Spd-2A (parent) organizes pericentriolar material during mitosis•Spd-2B (duplicate) organizes pericentriolar material during meiosis•The C-terminal tail domain of Spd-2A prevents meiotic function O’Neill et al. investigate a duplication of Spd-2 in Drosophila willistoni, finding that the ancestral Spd-2A functions in mitosis and the new gene Spd-2B functions in male meiosis. They show that Spd-2A lost its ability to function in meiosis due to changes in the C-terminal tail, pointing to a cell-type-specific regulat