RRC ID 54472
Author Matsumoto N, Nakanishi-Matsui M.
Title Proton pumping V-ATPase inhibitor bafilomycin A1 affects Rab7 lysosomal localization and abolishes anterograde trafficking of osteoclast secretory lysosomes.
Journal Biochem Biophys Res Commun
Abstract Osteoclast lysosomes secrete lytic enzymes into bone resorption lacunae, and sort the lysosomal proton pumping vacuolar-type ATPase (V-ATPase) to the plasma membrane to form the acidic environment required for bone digestion. The a3 isoform of V-ATPase is essential for outward trafficking of the secretory lysosomes and interacts physically with Rab7, a small GTPase that regulates trafficking of late endosomes and lysosomes, to recruit it to lysosomes. However, it is unclear whether organelle acidification by V-ATPase is required for the lysosome trafficking. Here, we showed that incubation of osteoclasts with the V-ATPase inhibitor bafilomycin A1 abolished the osteoclast-characteristic peripheral localization of secretory lysosomes, Rab7, and α-tubulin. Although bafilomycin A1 had little or no effect on Rab7 activation and its interaction with a3, treatment with the inhibitor significantly reduced the lysosomal localization of Rab7. Even constitutively active Rab7 did not localize to lysosomes in the presence of the inhibitor. These results suggest that organelle acidification by V-ATPase is required for localization of activated Rab7 to lysosomes.
Volume 510(3)
Pages 421-426
Published 2019-3-12
DOI 10.1016/j.bbrc.2019.01.118
PII S0006-291X(19)30147-0
PMID 30717974
MeSH Animals Biological Transport / drug effects Enzyme Inhibitors / pharmacology* HEK293 Cells Humans Lysosomes / chemistry Lysosomes / drug effects* Macrolides / pharmacology* Mice, Inbred C57BL Osteoclasts / chemistry Osteoclasts / drug effects* Tubulin / analysis Vacuolar Proton-Translocating ATPases / antagonists & inhibitors* rab GTP-Binding Proteins / analysis* rab7 GTP-Binding Proteins
IF 2.705
Times Cited 3
Mice RBRC04421
Human and Animal Cells 293T(RCB2202)