Rab1 and Syntaxin 17 regulate hematopoietic homeostasis through β-integrin trafficking in Drosophila

• Published in: Journal of genetics and genomics 2025-01, Vol.52 (1), p.51-65
• Main Authors: Luo, Fangzhou, Sui, Luwei, Sun, Ying, Lai, Zhixian, Zhang, Chengcheng, Zhang, Gaoqun, Bi, Bing, Yu, Shichao, Jin, Li Hua
• Format: Article
• Language: English
• Subjects: Drosophila; Hematopoiesis; Lymph gland; Rab1; Syntaxin 17; β-integrin
• ISSN: 1673-8527
• DOI: 10.1016/j.jgg.2024.11.001

Hematopoiesis is crucial for organismal health, and Drosophila serves as an effective genetic model due to conserved regulatory mechanisms with vertebrates. In larvae, hematopoiesis primarily occurs in the lymph gland, which contains distinct zones, including the cortical zone, intermediate zone, medullary zone, and posterior signaling center (PSC). Rab1 is vital for membrane trafficking and maintaining the localization of cell adhesion molecules, yet its role in hematopoietic homeostasis is not fully understood. This study investigates the effects of Rab1 dysfunction on β-integrin trafficking within circulating hemocytes and lymph gland cells. Rab1 impairment disrupts the endosomal trafficking of β-integrin, leading to its abnormal localization on cell membranes, which promotes lamellocyte differentiation and altered progenitor dynamics in circulating hemocytes and lymph glands, respectively. We also show that the mislocalization of β-integrin was dependent on the adhesion protein DE-cadherin. The reduction of β-integrin at cell boundaries in PSC cells leads to fewer PSC cells and lamellocyte differentiation. Furthermore, Rab1 regulates the trafficking of β-integrin via the Q-SNARE protein Syntaxin 17 (Syx17). Our findings indicate that Rab1 and Syx17 regulate distinct trafficking pathways for β-integrin in different hematopoietic compartments and maintain hematopoietic homeostasis of Drosophila.