News from the Institute

The serine/threonine kinase mTORC1 regulates cellular homeostasis in response to many cues such as nutrient status and energy level. Amino acids induce mTORC1 activation on lysosomes via the small Rag GTPases and the Ragulator complex, thereby controlling protein translation and cell growth.

As reported in Molecular and Cellular Biology the group of Dr. Christian Behrends identified the human 11-pass transmembrane protein SLC38A9 as a novel component of the Rag-Ragulator complex on lysosomes.

ALS (Amyotrophic lateral sclerosis ) is a devastating disease characterized by loss of motor neurons and neurodegeneration, usually leading to death within 3-4 years.

Despite being classified as rare disease, public awareness is very high, fueled by celebrity patients like Stephen Hawking and culminating in last years’ Ice Bucket Challenge, the first charity campaign with global impact. Still, there is no treatment for ALS, despite intensive research in the field.

Researchers from IBC2 and BMLS have now made a major step to a better understanding of the genes causing ALS.

The CEF Macromolecular Complexes approved funding for the proposal of Masato Akutsu, Christian Behrends, Vladimir Rogov and Volker Dötsch on the spatio-temporal regulation of protein complexes by the family of human ATG8 proteins.

By employing highly complementary structural, biophysical, biochemical and cell biological approaches this young team of researchers seeks to understand the role of the ubiquitin-like ATG8 proteins as reversible, membrane-bound scaffolds that help organizing protein and protein complexes spatially to control cellular pathways other than autophagy.

The research program is supported with 300.000 Euro for two years starting June 2015.

Spatio-temporal control is critical for RAC1 signaling. In this week’s online issue of Molecular Cell the group of Dr. Christian Behrends report the identification of CUL3-KBTBD6/KBTBD7 as ubiquitin ligase that locally regulates the abundance of the guanine exchange factor TIAM1.

Furthermore, membrane targeting of CUL3-KBTBD6/KBTBD7 is mediated by GABARAP proteins, thereby establishing functions of this subfamily of human ATG8 proteins beyond autophagy and membrane trafficking.

As reported in this month’s issue 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.