Involvement of l-afadin, but not s-afadin, in the formation of puncta adherentia junctions of hippocampal synapse

Publication date: Available online 30 June 2018Source: Molecular and Cellular NeuroscienceAuthor(s): Tomohiko Maruo, Shotaro Sakakibara, Muneaki Miyata, Yu Itoh, Souichi Kurita, Kenji Mandai, Takuya Sasaki, Yoshimi TakaiAbstractA hippocampal mossy fiber synapse has a complex structure in which presynaptic boutons attach to the dendritic trunk by puncta adherentia junctions (PAJs) and wrap multiply-branched spines, forming synaptic junctions. It was previously shown that afadin regulates the formation of the PAJs cooperatively with nectin-1, nectin-3, and N-cadherin. Afadin is a nectin-binding protein with two splice variants, l-afadin and s-afadin: l-afadin has an actin filament-binding domain, whereas s-afadin lacks it. It remains unknown which variant is involved in the formation of the PAJs or how afadin regulates it. We showed here that re-expression of l-afadin, but not s-afadin, in the afadin-deficient cultured hippocampal neurons in which the PAJ-like structure was disrupted, restored this structure as estimated by the accumulation of N-cadherin and αΝ-catenin. The l-afadin mutant, in which the actin filament-binding domain was deleted, or the l-afadin mutant, in which the αΝ-catenin-binding domain was deleted, did not restore the PAJ-like structure. Both l-afadin and s-afadin have the same αΝ-catenin-binding domain, but s-afadin less efficiently recruited αN-catenin to form the PAJ-like structure than l-afadin, although l-afadin showed this activity. These resu...

Source: Molecular and Cellular Neuroscience - July 5, 2018 Category: Neuroscience Source Type: research