M Dolores Martín-de-Saavedra, Marc Dos Santos, Lorenza Culotta, Olga Varea, Benjamin P Spielman, Euan Parnell, Marc P Forrest, Ruoqi Gao, Sehyoun Yoon, Emmarose McCoig, Hiba A Jalloul, Kristoffer Myczek, Natalia Khalatyan, Elizabeth A Hall, Liam S Turk, Antonio Sanz-Clemente, Davide Comoletti, Stefan F Lichtenthaler, Jeffrey S Burgdorf, Maria V Barbolina, Jeffrey N Savas, Peter Penzes
Although many neuronal membrane proteins undergo proteolytic cleavage, little is known about the biological significance of neuronal ectodomain shedding (ES). Here, we show that the neuronal sheddome is detectable in human cerebrospinal fluid (hCSF) and is enriched in neurodevelopmental disorder (NDD) risk factors. Among shed synaptic proteins is the ectodomain of CNTNAP2 (CNTNAP2-ecto), a prominent NDD risk factor. CNTNAP2 undergoes activity-dependent ES via MMP9 (matrix metalloprotease 9), and CNTNAP2-ecto levels are reduced in the hCSF of individuals with autism spectrum disorder...
February 16, 2022: Neuron