PD map update – June’16 edition

We are proud to announce the June'16 edition of the PD map. This release can be dubbed as "the big LRRK2 edition". We've integrated the outcomes LRRK2 curation workshop and more. Take a look.

LRRK2 curation workshop

In April we were honored to welcome Prof. Mark Cookson, from NIAs Laboratory of Neurogenetics to our PD map curation workshop. We were also kindly supported by our collaborators from Sanofi, France, Philippe Bertrand and Marlen Weber, and researchers from the LSCB, Sarah Nickels, Jonas Walter, Silvia Bolognin, Lisa Smits, Laura Gonzalez Cano, Anna Monzel, Simone Larsen, Clara Berenguer and Emanuel Berger

We focused on the role LRRK2 and its mutations in the molecular mechanisms of PD. There are a fair number of relevant pathways modulated by LRRK2 and we had a busy day going through them systematically. In the end, the PD map got new interactions in the areas of:

- microtubules and axonal transport, including LRRK2 interactions with tubulin, Wnt signaling and GSK3B

- pathways dedicated specifically to LRRK2 activity, emphasizing its interactions with trans-Golgi network, exosomes and formation of inclusion bodies

- actin filament organization, containing a detailed description of factors governing actin dynamics, including WASH complex and ROCK signaling

- mitochondrial fusion and fission, including interaction with DNM1L (DRP1)

- neuroinflammation and microglia signaling

- regulation of protein translation

- vesicle dynamics and interactions with a number of RAB proteins

You can simply type "LRRK2" in the search field to have a detailed overview.

 

Mitochondria

We've added mechanisms implicating VPS35 in DNM1L recycling via mitochondria derived vesicles (MDVs). Formation and degradation of MDVs is considered to be an additional quality check of mitochondria before mitophagy. We wrote about MDVs earlier (Faster than mitophagy), now they are on the map. Moreover, the layout of mitochondria was improved, featuring separate areas dedicated to OXPHOS, mitophagy, and fission-fusion-apoptosis dynamics. The area of "Fatty acid and ketone body metabolism" was moved to a dedicated submap.

 

Neuroinflammation

Microglial gene transcription mechanisms are now represented in more details in a microglial nucleus, including targets of NFkB and NFAT. M1 microglial activity features new interactions, describing its activity in more detail. Moreover, the layout of resting, M1 and M2 microglia has changed to better reflect specificities of these states and their transitions.

In this update the PD map grew by 113 publications and 83 new LRRK2 instances. Many thanks to the participants of the LRRK2 curation workshop! Particular thanks go to Stephan Gebel, who put the majority of these LRRK2 puzzle blocks together.

 

Marek Ostaszewski

Curator/Developer

 

 

P.S. If you are interested , you can join our next PD map workshop held during the 3rd International Parkinson’s Disease Symposium in October 2016.

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