MENTHO, a MLN64 homologue devoid of the START domain.
MLN64 is a late endosomal membrane protein containing a carboxyl-terminal cholesterol binding START domain and is presumably involved in intracellular cholesterol transport. In the present study, we have cloned a human cDNA encoding a novel protein that we called MENTHO as an acronym for MLN64 N-terminal domain homologue because this protein is closely related to the amino-terminal half of MLN64. MLN64 and MENTHO share 70% identity and 83% similarity in an original protein domain encompassing 171 amino acids that we designated as the MENTAL (MLN64 N-terminal) domain. By translation initiation scanning MENTHO is synthesized as two isoforms of 234 (alpha) and 227 (beta) amino acids that can be phosphorylated. As MLN64, MENTHO is ubiquitously expressed and is located in the membrane of late endosomes, its amino and carboxyl-terminal extremities projecting toward the cytoplasm. We show that MENTHO overexpression does not rescue the Niemann-Pick type C lipid storage phenotype. However, MENTHO overexpression alters severely the endocytic compartment by leading at steady state to the accumulation of enlarged endosomes. These results indicate that in addition to its previously established function in addressing and anchoring proteins to the membrane of late endosomes, the MENTAL domain possesses an intrinsic biological function in endocytic transport.
Alpy
Fabien
F
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS/INSERM/ Université Louis Pasteur, BP 10142, 67404 Illkirch, C. U. de Strasbourg, France.
Wendling
Corinne
C
Rio
Marie-Christine
MC
Tomasetto
Catherine
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016466:CHO Cells; D002352:Carrier Proteins; D003001:Cloning, Molecular; D006224:Cricetinae; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D015723:Gene Library; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D002352:Carrier Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; C105684:STARD3 protein, human; C471300:STARD3NL protein, human