LAUSR

The ubiquitously expressed transmembrane enzyme Na,K‐ATPase (NKA) is vital in maintaining functionality of cells. The association of α‐ and β‐subunits is believed to be essential for forming a functional enzyme. In the large milkweed bug Oncopeltus fasciatus four α1‐paralogs and four β‐subunits exist that can associate into NKA complexes. This diversity raises the question of possible tissue‐specific distribution and function. While the α1‐subunits are known to modulate cardenolide‐resistance and ion‐transport efficiency, the functional importance of the β‐subunits needed further investigation. We here characterize all four different β‐subunits at the cellular, tissue, and whole organismal scales. A knockdown of different β‐subunits heavily interferes with molting success resulting in strongly hampered phenotypes. The failure of ecdysis might be related to disrupted septate junction (SJ) formation, also reflected in β2‐suppression‐induced alteration in tracheal morphology. Our data further suggest the existence of isolated β‐subunits forming homomeric or β‐heteromeric complexes. This possible standalone and structure‐specific distribution of the β‐subunits predicts further, yet unknown pump‐independent functions. The different effects caused by β knockdowns highlight the importance of the various β‐subunits to fulfill tissue‐specific requirements.