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Lrrk2 phagocytosis

Kwang Soo Kim, Paul C Marcogliese, Jungwoo Yang, Steve M Callaghan, Virginia Resende, Elizabeth Abdel-Messih, Connie Marras, Naomi P Visanji, Jana Huang, Michael G Schlossmacher, Laura Trinkle-Mulcahy, Ruth S Slack, Anthony E Lang, David S Park
Leucine-rich repeat kinase 2 ( LRRK2 ) has been implicated in both familial and sporadic Parkinson's disease (PD), yet its pathogenic role remains unclear. A previous screen in Drosophila identified Scar/WAVE (Wiskott-Aldrich syndrome protein-family verproline) proteins as potential genetic interactors of LRRK2 Here, we provide evidence that LRRK2 modulates the phagocytic response of myeloid cells via specific modulation of the actin-cytoskeletal regulator, WAVE2. We demonstrate that macrophages and microglia from LRRK2-G2019S PD patients and mice display a WAVE2-mediated increase in phagocytic response, respectively...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
Dieter Waschbüsch, Helen Michels, Swantje Strassheim, Edith Ossendorf, Daniel Kessler, Christian Johannes Gloeckner, Angelika Barnekow
Leucine-rich repeat kinase 2 (LRRK2) is a multi-domain 280 kDa protein that is linked to Parkinson's disease (PD). Mutations especially in the GTPase and kinase domains of LRRK2 are the most common causes of heritable PD and are also found in sporadic forms of PD. Although the cellular function of LRRK2 is largely unknown there is increasing evidence that these mutations cause cell death due to autophagic dysfunction and mitochondrial damage. Here, we demonstrate a novel mechanism of LRRK2 binding and transport, which involves the small GTPases Rab32 and Rab38...
2014: PloS One
Yvan Wenger, Wanda Buzgariu, Silke Reiter, Brigitte Galliot
The impact of injury-induced immune responses on animal regenerative processes is highly variable, positive or negative depending on the context. This likely reflects the complexity of the innate immune system that behaves as a sentinel in the transition from injury to regeneration. Early-branching invertebrates with high regenerative potential as Hydra provide a unique framework to dissect how injury-induced immune responses impact regeneration. A series of early cellular events likely require an efficient immune response after amputation, as antimicrobial defence, epithelial cell stretching for wound closure, migration of interstitial progenitors toward the wound, cell death, phagocytosis of cell debris, or reconstruction of the extracellular matrix...
August 2014: Seminars in Immunology
Daniel F Marker, Jenna M Puccini, Taryn E Mockus, Justin Barbieri, Shao-Ming Lu, Harris A Gelbard
BACKGROUND: Human Immunodeficiency Virus-1 (HIV-1) associated neurocognitive disorders (HANDs) are accompanied by significant morbidity, which persists despite the use of combined antiretroviral therapy (cART). While activated microglia play a role in pathogenesis, changes in their immune effector functions, including phagocytosis and proinflammatory signaling pathways, are not well understood. We have identified leucine-rich repeat kinase 2 (LRRK2) as a novel regulator of microglial phagocytosis and activation in an in vitro model of HANDs, and hypothesize that LRRK2 kinase inhibition will attenuate microglial activation during HANDs...
November 29, 2012: Journal of Neuroinflammation
Agnès Gardet, Yair Benita, Chun Li, Bruce E Sands, Isabel Ballester, Christine Stevens, Joshua R Korzenik, John D Rioux, Mark J Daly, Ramnik J Xavier, Daniel K Podolsky
LRRK2 was previously identified as a defective gene in Parkinson's disease, and it is also located in a risk region for Crohn's disease. In this study, we aim to determine whether LRRK2 could be involved in immune responses. We show that LRRK2 expression is enriched in human immune cells. LRRK2 is an IFN-γ target gene, and its expression increased in intestinal tissues upon Crohn's disease inflammation. In inflamed intestinal tissues, LRRK2 is detected in the lamina propria macrophages, B-lymphocytes, and CD103-positive dendritic cells...
November 1, 2010: Journal of Immunology: Official Journal of the American Association of Immunologists
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