![activation repair activation repair](https://4.bp.blogspot.com/-UdD6tj_sUQg/Vn5rFiH2hFI/AAAAAAAAD1g/4idopdovqjQ/s1600/how+to+remove+windows+xp+activation+message.jpg)
Rab8A recruitment was visualised by immunofluorescence. (E) Macrophages were treated with the GSK LRRK2 kinase inhibitor (1 μM) and infected with Ca or (F) Lm for 60 min. Macrophages were transfected with EGFP‐Rab8A, treated with 1 μM GSK2578215A (GSK inh) and infected with Mtb for 24 h. (B) WT and LRRK2 KO macrophages were infected with Ca and (C) Lm for 60 min. WT and LRRK2 KO macrophages were transfected with EGFP‐Rab8A and infected with Mtb for 24 h. Source data are available online for this figure. One‐way ANOVA followed by Dunnett's test against DMSO control. Data represent the mean + SEM of three independent biological replicates. Rab8A pT72 and LRRK2 pS935 phosphorylation was analysed by Western blot and quantified by densitometry. RAW264.7 macrophages were pre‐treated with 1 μM GSK2578215A (GSK inh) or 0.1 μM MLi‐2 and left uninfected or infected with (G) Mtb for 24 h, (H) Ca or (I) Lm for 120 min. Rab8A pT72 and LRRK2 pS935 phosphorylation was analysed by Western blot. WT and LRRK2 KO macrophages were left uninfected or infected with (D) Mtb for 24 h, (E) Ca or (F) Lm for 120 min. RAW264.7 macrophages were left uninfected or infected with (A) Mycobacterium tuberculosis (Mtb), (B) C. albicans (Ca) or (C) L. monocytogenes (Lm) for the indicated time, and Rab8A pT72, Rab10 pT73 and LRRK2 pS935 levels were analysed by Western blot. Published under the terms of the CC BY 4.0 license. LRRK2 Parkinson's disease endolysosomal damage lysosomes tuberculosis. Altogether, this work indicates that LRRK2 regulates endolysosomal homeostasis by controlling the balance between membrane repair and organelle replacement, uncovering an unexpected function for LRRK2, and providing a new link between membrane damage and PD. These observations are recapitulated in macrophages from PD patients where pathogenic LRRK2 gain-of-function mutations result in the accumulation of endolysosomes which are positive for the membrane damage marker Galectin-3. Conversely, in the absence of LRRK2 and Rab8A, damaged endolysosomes are targeted to lysophagy. LRRK2 recruits the Rab GTPase Rab8A to damaged endolysosomes as well as the ESCRT-III component CHMP4B, thereby favouring ESCRT-mediated repair. Here, we show that the Parkinson's disease (PD)-related kinase LRRK2 is activated in macrophages by pathogen- or sterile-induced endomembrane damage. However, the signals regulating the decision for repair or lysophagy are poorly characterised. Cells respond to endolysosome damage by either repairing the damage or targeting damaged endolysosomes for degradation via lysophagy.