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Vol. 10, Issue 4, 1277-1287, April 1999

Transmembrane Insertion of the Toxoplasma gondii GRA5 Protein Occurs after Soluble Secretion into the Host Cell

Laurence Lecordier,^* Corinne Mercier,^* L. David Sibley, and Marie-France Cesbron-Delauw^*§

 ^*Mécanismes Moléculaires de la Pathogénèse des Sporozoaires, Institut Pasteur de Lille, Institut de Biologie de Lille, 59019 Lille cedex, France; and  Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri

The intracellular parasite Toxoplasma gondii resides within a specialized compartment, the parasitophorous vacuole (PV), that resists fusion with host cell endocytic and lysosomal compartments. The PV is extensively modified by secretion of parasite proteins, including the dense granule protein GRA5 that is specifically targeted to the delimiting membrane of the PV (PVM). We show here that GRA5 is present both in a soluble form and in hydrophobic aggregates. GRA5 is secreted as a soluble form into the PV after which it becomes stably associated with the PVM. Topological studies demonstrated that GRA5 was inserted into the PVM as a transmembrane protein with its N-terminal domain extending into the cytoplasm and its C terminus in the vacuole lumen. Deletion of 8 of the 18 hydrophobic amino acids of the single predicted transmembrane domain resulted in the failure of GRA5 to associate with the PVM; yet it remained correctly packaged in the dense granules and was secreted as a soluble protein into the PV. Collectively, these studies demonstrate that the secretory pathway in Toxoplasma is unusual in two regards; it allows soluble export of proteins containing typical transmembrane domains and provides a mechanism for their insertion into a host cell membrane after secretion from the parasite.

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^§   Corresponding author. E-mail address: mcesbron{at}infobiogen.fr.
   Present address: Laboratory of Molecular Parasitology, Université Libre de Bruxelles, Rhode Saint Genese, Belgium.

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Molecular Biology of the Cell
Vol. 10, 1277-1287, April 1999
Copyright © 1999 by The American Society for Cell Biology

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