Expression analyses and interaction with the anaphase promoting complex protein Apc2 suggest a role for inversin in primary cilia and involvement in the cell cycle.
Homozygous inv mice lack a functional inversin protein and exhibit situs inversus plus severe cystic changes in the kidney and pancreas. Although the inversin sequence has provided few clues to its function, we and others have previously identified calmodulin as a binding partner. We now provide evidence that inversin interacts with the anaphase promoting complex protein Apc2. As expected of an Apc2 target, inversin possesses D-boxes and site-directed mutagenesis of the well-conserved D-box residues abrogates inversin-Apc2 interaction. An inversin-specific antibody reveals a dynamic expression pattern throughout the cell cycle and strong expression in the primary cilia of renal epithelium. Our data support a role for inversin in primary cilia and involvement in the cell cycle. Mutations of the proteins polaris, cystin and polycystin-2 which are expressed in renal epithelium primary cilia, lead to renal cystic changes. Aberrant cell proliferation is also involved in cyst development. The data reported here suggest that inversin may provide a link between these two mechanisms.
Morgan
David
D
Institute of Human Genetics, University of Newcastle, International Centre for Life, Central Parkway, Newcastle upon Tyne, UK.
Eley
Lorraine
L
Sayer
John
J
Strachan
Tom
T
Yates
Laura M
LM
Craighead
A Scott
AS
Goodship
Judith A
JA
D020816:Amino Acid Motifs; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D064190:Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome; D002453:Cell Cycle / Q000502:physiology*; D002923:Cilia / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D052177:Kidney Diseases, Cystic / Q000235:genetics / Q000378:metabolism; D008025:Ligases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism*; D014157:Transcription Factors; D020798:Two-Hybrid System Techniques; D043743:Ubiquitin-Protein Ligase Complexes
C491947:Invs protein, mouse; D011506:Proteins; D014157:Transcription Factors; D043743:Ubiquitin-Protein Ligase Complexes; C577341:Anapc2 protein, mouse; D064173:Anaphase-Promoting Complex-Cyclosome; D064190:Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome; D008025:Ligases