Two PI 3-kinases and one PI 3-phosphatase together establish the cyclic waves of phagosomal PtdIns(3)P critical for the degradation of apoptotic cells.
Details
Serval ID
serval:BIB_7D651956733B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Two PI 3-kinases and one PI 3-phosphatase together establish the cyclic waves of phagosomal PtdIns(3)P critical for the degradation of apoptotic cells.
Journal
PLoS biology
ISSN
1545-7885 (Electronic)
ISSN-L
1544-9173
Publication state
Published
Issued date
01/2012
Peer-reviewed
Oui
Volume
10
Number
1
Pages
e1001245
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Phosphatidylinositol 3-phosphate (PtdIns(3)P) is a signaling molecule important for many membrane trafficking events, including phagosome maturation. The level of PtdIns(3)P on phagosomes oscillates in two waves during phagosome maturation. However, the physiological significance of such oscillation remains unknown. Currently, the Class III PI 3-kinase (PI3K) Vps34 is regarded as the only kinase that produces PtdIns(3)P in phagosomal membranes. We report here that, in the nematode C. elegans, the Class II PI3K PIKI-1 plays a novel and crucial role in producing phagosomal PtdIns(3)P. PIKI-1 is recruited to extending pseudopods and nascent phagosomes prior to the appearance of PtdIns(3)P in a manner dependent on the large GTPase dynamin (DYN-1). PIKI-1 and VPS-34 act in sequence to provide overlapping pools of PtdIns(3)P on phagosomes. Inactivating both piki-1 and vps-34 completely abolishes the production of phagosomal PtdIns(3)P and disables phagosomes from recruiting multiple essential maturation factors, resulting in a complete arrest of apoptotic-cell degradation. We have further identified MTM-1, a PI 3-phosphatase that antagonizes the activities of PIKI-1 and VPS-34 by down-regulating PtdIns(3)P on phagosomes. Remarkably, persistent appearance of phagosomal PtdIns(3)P, as a result of inactivating mtm-1, blocks phagosome maturation. Our findings demonstrate that the proper oscillation pattern of PtdIns(3)P on phagosomes, programmed by the coordinated activities of two PI3Ks and one PI 3-phosphatase, is critical for phagosome maturation. They further shed light on how the temporally controlled reversible phosphorylation of phosphoinositides regulates the progression of multi-step cellular events.
Keywords
Animals, Apoptosis, Caenorhabditis elegans/cytology, Caenorhabditis elegans/enzymology, Caenorhabditis elegans/ultrastructure, Caenorhabditis elegans Proteins/metabolism, Down-Regulation, Enzyme Activation, Phagosomes/enzymology, Phagosomes/ultrastructure, Phosphatidylinositol 3-Kinases/metabolism, Phosphatidylinositol Phosphates/metabolism, Phosphoprotein Phosphatases/metabolism, Protein Binding, rab GTP-Binding Proteins/metabolism
Pubmed
Web of science
Publisher's website
Open Access
Yes
Create date
08/12/2023 10:45
Last modification date
09/12/2023 8:03