The tubby family proteins

Saikat Mukhopadhyay, Peter K. Jackson

Research output: Contribution to journalReview article

53 Scopus citations

Abstract

The tubby mouse shows a tripartite syndrome characterized by maturity-onset obesity, blindness and deafness. The causative gene Tub is the founding member of a family of related proteins present throughout the animal and plant kingdoms, each characterized by a signature carboxy-terminal tubby domain. This domain consists of a β barrel enclosing a central β helix and binds selectively to specific membrane phosphoinositides. The vertebrate family of tubby-like proteins (TULPs) includes the founding member TUB and the related TULPs, TULP1 to TULP4. Tulp1 is expressed in the retina and mutations in TULP1 cause retinitis pigmentosa in humans; Tulp3 is expressed ubiquitously in the mouse embryo and is important in sonic hedgehog (Shh)-mediated dorso-ventral patterning of the spinal cord. The amino terminus of these proteins is diverse and directs distinct functions. In the best-characterized example, the TULP3 amino terminus binds to the IFT-A complex, a complex important in intraflagellar transport in the primary cilia, through a short conserved domain. Thus, the tubby family proteins seem to serve as bipartite bridges through their phosphoinositide-binding tubby and unique amino-terminal functional domains, coordinating multiple signaling pathways, including ciliary G-protein-coupled receptor trafficking and Shh signaling. Molecular studies on this functionally diverse protein family are beginning to provide us with remarkable insights into the tubby-mouse syndrome and other related diseases

Original languageEnglish (US)
Article number225
JournalGenome biology
Volume12
Issue number6
DOIs
StatePublished - Jun 28 2011

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology

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