Hypothesis paper: the development of a regulatory layer in P2B autoinhibited Ca²⁺-ATPases may have facilitated plant terrestrialization and animal multicellularization

ABSTRACT

With the appearance of plants and animals, new challenges emerged. These multicellular eukaryotes had to solve for example the difficulties of multifaceted communication between cells and adaptation to new habitats. In this paper, we are looking for one piece of the puzzle that made the development of complex multicellular eukaryotes possible with a focus on regulation of P2B autoinhibited Ca²⁺-ATPases. P2B ATPases pump Ca²⁺ out of the cytosol at the expense of ATP hydrolysis, and thereby maintain a steep gradient between the extra- and intracytosolic compartments which is utilized for Ca²⁺-mediated rapid cell signaling. The activity of these enzymes is regulated by a calmodulin (CaM)-responsive autoinhibitory region, which can be located in either termini of the protein, at the C-terminus in animals and at the N-terminus in plants. When the cytoplasmic Ca²⁺ level reaches a threshold, the CaM/Ca²⁺ complex binds to a calmodulin-binding domain (CaMBD) in the autoinhibitor, which leads to the upregulation of pump activity. In animals, protein activity is also controlled by acidic phospholipids that bind to a cytosolic portion of the pump. Here, we analyze the appearance of CaMBDs and the phospholipid-activating sequence and show that their evolution in animals and plants was independent. Furthermore, we hypothesize that different causes may have initiated the appearance of these regulatory layers: in animals, it is linked to the appearance of multicellularity, while in plants it co-occurs with their water-to-land transition.

KEYWORDS:

• Evolution
• P2B ATPase
• calmodulin-binding domain
• phospholipid-binding domain
• multicellularity
• terrestrialization

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

M.P. developed the core idea, A.S. did the phylogenetic analysis, M.P. supervised the work, A.S. and M.P. wrote the manuscript.

Data availability statement

All data supporting the findings of this study are included in this article, its Supplementary Information, and the Supplementary Data file. Any other data will be made available upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15592324.2023.2204284

Additional information

Funding

This work was supported by grants from the Danish National Research Foundation (PUMPkin; M.P.) the Carlsberg Foundation (RaisingQuinoa; project number CF18-1113; M.P.), the Innovation Fund Denmark (LESSISMORE and DEEPROOTS; M.P.), and the Novo Nordisk Foundation (NovoCrops; project number 2019OC53580; M.P.).