Tubby proteins: the plot thickens

Publisher Website
Google Scholar
Abstract
TUB is the founding member of the tubby-like proteins, or TULPs. TULPs are found in multicellular organisms from both the plant and animal kingdoms, which indicates an ancient and fundamental function. The TULP family of proteins has neuronal expression patterns in the retina and cochlea, and throughout the brain. TULPs have been shown to have a role in obesity, sensoneuronal degeneration, and development; and ablation of certain TULPs has been shown to be responsible for obesity and retinitis pigmentosa. The TULPs are characterized by a highly conserved domain of about 260 amino acids — the 'tubby' domain — which is located at the carboxyl terminus of all TULP-family proteins. The tubby domain has been shown to bind double-stranded DNA, and certain amino-terminal splice forms of the mouse TUB protein have been shown to activate transcription. Furthermore, the TUB protein has been shown to localize to both the cell membrane and the nucleus. These data have led to the hypothesis that TULPs might function in transcription. Compelling evidence shows that TULPs respond to signals from activated heterotrimeric G-proteins of the Gαq/11 family, which function through a phospholipase-Cβ-dependent pathway to mediate translocation of TUB from the plasma membrane to the nucleus. Other evidence also implicates TUB in neuronal synapse function, and rhodopsin transport. This variety of seemingly disparate results, when reconciled, might place TULPs at a central point in the integration of a number of cellular signals.