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PLEKHM1: A multifunctional adaptor for the endolysosomal system

January 2015. As reported in this month’s issues of Molecular Cell and Cell Host & Microbe, an international team of researchers led by Prof. Ivan Dikic has shed light on the molecular function of the protein PLEKHM1, that has previously been shown to regulate bone density in humans and rats. The team has identified two novel functions for the protein that are important for human disease; firstly, facilitating the removal of toxic protein aggregates and preventing their accumulation, which is relevant for diseases such as Parkinson’s. Secondly, controlling the intracellular growth of invading pathogens such as Salmonella. Both studies provide insight into the molecular mechanisms of cellular processes with high relevance to human diseases, and give rise to potential targets for therapeutic intervention.

Preview for Molecular Cell article here
Molecular Cell
article here
Cell Host & Microbe article here


Ivan Dikic
Institute of Biochemistry II
Buchmann Institute for Molecular Life Sciences
Goethe University Frankfurt
Frankfurt (Main), Germany

Full references:

McEwan DG, Popovic D, Gubas A, Terawaki S, Suzuki H, Stadel D, Coxon FP, Stegmann DMd, Bhogaraju S, Maddi K, Kirchof A, Gatti E, Helfrich MH, Wakatsuki S, Behrends C, Pierre P, Dikic I (2015) PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and LC3/GABARAP proteins. Mol Cell 57:39–54

McEwan DG, Richter B, Claudi B, Wigge C, Wild P, Farhan H, McGourty K, Coxon FP, Franz-Wachtel M, Perdu B, Akutsu M, Habermann A, Kirchof A, Helfrich MH, Odgren PR, Hul WV, Frangakis AS, Rajalingam K, Macek B, Holden DW, Bumann D, Dikic I (2015) PLEKHM1 regulates Salmonella-containing vacuole biogenesis and infection. Cell Host Microbe:17:58–71