This website uses cookies so that we can provide you with the best user experience possible. Cookie information is stored in your browser and performs functions such as recognising you when you return to our website and helping our team to understand which sections of the website you find most interesting and useful.
Catalog
ASAP is committed to accelerating the pace of discovery and informing a path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. We’ve created this catalog to showcase the research outputs and tools developed by ASAP-funded programs.
Article
Mechanism of human PINK1 activation at the TOM complex in a reconstituted system
Preprint: The authors demonstrate an essential role of the pore-containing subunit TOM40 and its structurally associated subunits TOM7 and TOM22 for PINK1 activation. These molecular findings will aid in the development of small molecule activators of PINK1 as a therapeutic strategy for PD.
Dataset
Primary data associated with the manuscript 10.1126/science.adi9926 (“Rab29-dependent asymmetrical activation of leucine-rich repeat kinase 2”)
Primary data associated with the manuscript “Rab29-dependent asymmetrical activation of leucine-rich repeat kinase 2” (Hanwen Zhu, Francesca Tonelli, Martin Turk, Alan Prescott, Dario R. Alessi, Ji Sun). These include immunoblotting data and their quantitation, representative confocal microscopy images, and quantitation and statistical analysis of confocal microscopy images.
Teams
Themes
Article
Global ubiquitylation analysis of mitochondria in primary neurons identifies endogenous Parkin targets following activation of PINK1
Published: Loss-of-function mutations in Parkin cause disruption of mitophagy and are associated with PD. Yet, much of the biology surrounding Parkin function has taken place in artificial cell systems. The authors used human neurons to identify and validate 22 protein targets of Parkin, providing a functional Parkin landscape in neuronal cells.
Themes
Article
Global ubiquitylation analysis of mitochondria in primary neurons identifies physiological Parkin targets following activation of PINK1
Published: Mutations in PINK1 and Parkin are implicated in PD via abherrant mitophagy. The authors identified ubiquitylated substrates of endogenous Parkin in mouse neurons by proteomic analysis. They identified and validated 22 protein targets of Parkin that are conserved in human neurons providing a functional Parkin landscape in neuronal cells. View original preprint.
Themes
Article
PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074, and Thr1075) within the CORB GTPase domain
Leucine-rich-repeat-kinase 1 (LRRK1) and its homologue LRRK2 are multidomain kinases possessing a ROC-CORA-CORB containing GTPase domain and phosphorylate distinct Rab proteins. LRRK1 loss of function mutations cause the bone disorder osteosclerotic metaphyseal dysplasia, whereas LRRK2 missense mutations that enhance kinase activity cause PD. Here, the authors study the mechanism controlling LRRK1 activity and reveal a novel unexpected activation mechanism. View preprint.
Themes
Dataset
Mass spectrometry proteomic data supporting the PPM1H/Rab8A crosslinking study described in doi: 10.15252/embr.202152675
Raw data associated with DOI: 10.15252/embr.202152675
Teams
Themes
Article
Structural basis for the specificity of PPM1H phosphatase for Rab GTPases
Published: LRRK2 acts by adding a phosphate group to enzymes known as Rab GTPases, which causes new biological events. The authors analyzed the structure of an enzyme, PPM1H, that counteracts LRRK2 by removing the phosphate group it adds to Rab GTPases. View original preprint.
Teams
Themes
Article
Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain
Published: Pathogenic mutations in LRRK2 are known to cause loss of primary cilia in neurons. The authors show that cilia loss is seen very early in mice harboring the most common LRRK2 mutation. Further, they show that this loss of cilia in astrocytes disrupted signaling pathways required for dopamine neuron maintenance. View original preprint.
Teams
Themes
Dataset
Structural basis for the specificity of PPM1H phosphatase for Rab GTPases Figures
Raw data associated with DOI: 10.15252/embr.202152675
Teams
Themes