PALLD Regulates Phagocytosis by Enabling Timely Actin Polymerization and Depolymerization

• Published in: The Journal of immunology (1950) Vol. 199; no. 5; pp. 1817 - 1826
• Main Authors: Sun, Hai-Min, Chen, Xin-Lei, Chen, Xin-Jie, Liu, Jin, Ma, Lie, Wu, Hai-Yan, Huang, Qiu-Hua, Xi, Xiao-Dong, Yin, Tong, Zhu, Jiang, Chen, Zhu, Chen, Sai-Juan
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 01.09.2017
• Subjects: Actin; Actins - metabolism; Animals; Cell Differentiation; Cell Line, Tumor; Cell Self Renewal; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Dendritic Cells - immunology; Depolymerization; Humans; Immunity, Innate; Immunoglobulins; Innate immunity; Leukemia; Leukemia, Myeloid, Acute - immunology; Mice; Mice, Inbred C57BL; Myeloid leukemia; Neoplastic Stem Cells - physiology; Oculocerebrorenal Syndrome - immunology; Opsonization; Phagocytes; Phagocytosis; Phagosomes - metabolism; Phosphatidylinositol 4,5-diphosphate; Phosphoproteins - genetics; Phosphoproteins - metabolism; Phosphoric Monoester Hydrolases - metabolism; Polymerization; Receptor Aggregation; Receptor density; Retinoic acid; Src protein; Tretinoin; Tretinoin - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1602018

PALLD is an actin cross-linker supporting cellular mechanical tension. However, its involvement in the regulation of phagocytosis, a cellular activity essential for innate immunity and physiological tissue turnover, is unclear. We report that is highly induced along with all- -retinoic acid-induced maturation of myeloid leukemia cells, to promote Ig- or complement-opsonized phagocytosis. PALLD mechanistically facilitates phagocytic receptor clustering by regulating actin polymerization and c-Src dynamic activation during particle binding and early phagosome formation. PALLD is also required at the nascent phagosome to recruit phosphatase oculocerebrorenal syndrome of Lowe, which regulates phosphatidylinositol-4,5-bisphosphate hydrolysis and actin depolymerization to complete phagosome closure. Collectively, our results show a new function for PALLD as a crucial regulator of the early phase of phagocytosis by elaborating dynamic actin polymerization and depolymerization.