How Gpm6a induces the formation of filopodia

FUCHSOVA, B.; ROSAS, N.M.; FRASCH, A. C.

Chicago

Congreso; Neuroscience 2019; 2019

Society for Neuroscience (SFN)

How Gpm6a induces theformation of filopodiaBackground:- Gpm6a is a neuronal membraneglycoprotein linked to pathological conditions such as depression,schizophrenia and bipolar disorder, claustrophobia and learning disability (Fuchsova,Neuroscience 2015; Boks, Am J Med Gen 2008; Greenwood, Biol Psychiatry2012; El-Kordi, Transl. Psychiatry 2013)- plays a role in differentprocesses of neuroplasticity and its oversexpression leads to the extensiveformation of filopodia (Alfonso, PNAS 2005; Fuchsova, J Biol Chem 2009; Formoso,J Neurochem 2015; Alvarez Juliá, J Neurochem 2016)- neuronal filopodia underliemorphogenetic events ranging from the initiation, extension, guidance andbranching of neuronal processes to the formation of synapsis- the mechanism that mediatesformation of filopodia by Gpm6a is not fully understood but we have showed thatit requires actin regulator coronin-1a (Coro1a). Moreover, Coro1acoimmunoprecipitates and colocalizes with Gpm6a in rat hippocampal neurons. (Fuchsova,Neuroscience 2015; Alvarez Juliá, J Neurochem 2016)Hypothesis: The cytoplasmic tails of Gpm6amediate its interaction with proteins that regulate intracellular signaling andthis interaction is crucial for the process of filopodium formation induced byGpm6a.Summary:- The formation of filopodiainduced by Gpm6a requires the C-terminal but no the N-terminal cytoplasmatictail- K250, K255, and E258 withinthe C-terminal cytoplasmatic tail were idenified as critical residues for thefilopodium formation induced by Gpm6a in hippocampal neurons- Mutant forms of Gpm6a thataffect filopodium formation display preferential localization to Lamp1-positive lysosomal structures in N2a cells- The C-terminal cytoplasmatictail of Gpm6a coimmunoprecipitates with Coro1a