In search of the still unknown function of FW2.2/CELL NUMBER REGULATOR, a major regulator of fruit size in tomato

Abstract The FW2.2 gene is associated with the major quantitative trait locus (QTL) governing fruit size in tomato, and acts by negatively controlling cell division during fruit development. FW2.2 belongs to a multigene family named the CELL NUMBER REGULATOR (CNR) family. CNR proteins harbour the uncharacterized PLAC8 motif made of two conserved cysteine-rich domains separated by a variable region that are predicted to be transmembrane segments, and indeed FW2.2 localizes to the plasma membrane. Although FW2.2 was cloned more than two decades ago, the molecular mechanisms of action remain unknown. In particular, how FW2.2 functions to regulate cell cycle and fruit growth, and thus fruit size, is as yet not understood. Here we review current knowledge on PLAC8-containing CNR/FWL proteins in plants, which are described to participate in organogenesis and the regulation of organ size, especially in fruits, and in cadmium resistance, ion homeostasis, and/or Ca2+ signalling. Within the plasma membrane FW2.2 and some CNR/FWLs are localized in microdomains, which is supported by recent data from interactomics studies. Hence FW2.2 and CNR/FWL could be involved in a transport function of signalling molecules across membranes, influencing organ growth via a cell to cell trafficking mechanism. The FW2.2 protein is a major regulator of fruit size in tomato. This review summarizes current knowledge of FW2.2 and its homologues to elucidate their still undeciphered cellular and molecular function in the regulation of organ size.