Open AccessA Functional Interaction Between Na,K-ATPase β2-Subunit/AMOG and NF2/Merlin Regulates Growth Factor Signaling in Cerebellar Granule Cells
Author(s) -
Alisa Litan,
Zhiqin Li,
Elmíra Tokhtaeva,
Patience Kelly,
Olga Vagin,
Sigrid A. Langhans
Publication year - 2019
Publication title -
molecular neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.569
H-Index - 111
eISSN - 1559-1182
pISSN - 0893-7648
DOI - 10.1007/s12035-019-1592-4
Subject(s) - microbiology and biotechnology , protein subunit , biology , signal transduction , hippo signaling pathway , scaffold protein , merlin (protein) , phosphorylation , chemistry , biochemistry , suppressor , gene
The Na,K-ATPase, consisting of a catalytic α-subunit and a regulatory β-subunit, is a ubiquitously expressed ion pump that carries out the transport of Na + and K + across the plasma membranes of most animal cells. In addition to its pump function, Na,K-ATPase serves as a signaling scaffold and a cell adhesion molecule. Of the three β-subunit isoforms, β 1 is found in almost all tissues, while β 2 expression is mostly restricted to brain and muscle. In cerebellar granule cells, the β 2 -subunit, also known as adhesion molecule on glia (AMOG), has been linked to neuron-astrocyte adhesion and granule cell migration, suggesting its role in cerebellar development. Nevertheless, little is known about molecular pathways that link the β 2 -subunit to its cellular functions. Using cerebellar granule precursor cells, we found that the β 2 -subunit, but not the β 1 -subunit, negatively regulates the expression of a key activator of the Hippo/YAP signaling pathway, Merlin/neurofibromin-2 (NF2). The knockdown of the β 2 -subunit resulted in increased Merlin/NF2 expression and affected downstream targets of Hippo signaling, i.e., increased YAP phosphorylation and decreased expression of N-Ras. Further, the β 2 -subunit knockdown altered the kinetics of epidermal growth factor receptor (EGFR) signaling in a Merlin-dependent mode and impaired EGF-induced reorganization of the actin cytoskeleton. Therefore, our studies for the first time provide a functional link between the Na,K-ATPase β 2 -subunit and Merlin/NF2 and suggest a role for the β 2 -subunit in regulating cytoskeletal dynamics and Hippo/YAP signaling during neuronal differentiation.