Inactivation of lmpA, encoding a LIMPII-related endosomal protein, suppresses the internalization and endosomal trafficking defects in profilin-null mutants

Profilin is a key phosphoinositide and actin-binding protein connecting and coordinating changes in signal transduction pathways with alterations in the actin cytoskeleton. Using biochemical assays and microscopic approaches, we demonstrate that profilin-null cells are defective in macropinocytosis,...

Full description

Saved in:
Bibliographic Details
Published in:Molecular biology of the cell 2000-06, Vol.11 (6), p.2019-2031
Main Authors: Temesvari, L, Zhang, L, Fodera, B, Janssen, K P, Schleicher, M, Cardelli, J A
Format: Article
Language:English
Subjects:
Biological Transport
CD36 Antigens - genetics
CD36 Antigens - physiology
Contractile Proteins
Endosomes - physiology
Exocytosis - physiology
Gene Deletion
Hydrolases - metabolism
Intracellular Fluid - metabolism
Microfilament Proteins - genetics
Microfilament Proteins - physiology
Phagocytosis - physiology
Pinocytosis - physiology
Profilins
Proteins - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Profilin is a key phosphoinositide and actin-binding protein connecting and coordinating changes in signal transduction pathways with alterations in the actin cytoskeleton. Using biochemical assays and microscopic approaches, we demonstrate that profilin-null cells are defective in macropinocytosis, fluid phase efflux, and secretion of lysosomal enzymes but are unexpectedly more efficient in phagocytosis than wild-type cells. Disruption of the lmpA gene encoding a protein (DdLIMP) belonging to the CD36/LIMPII family suppressed, to different degrees, most of the profilin-minus defects, including the increase in F-actin, but did not rescue the secretion defect. Immunofluorescence microscopy indicated that DdLIMP, which is also capable of binding phosphoinositides, was associated with macropinosomes but was not detected in the plasma membrane. Also, inactivation of the lmpA gene in wild-type strains resulted in defects in macropinocytosis and fluid phase efflux but not in phagocytosis. These results suggest an important role for profilin in regulating the internalization of fluid and particles and the movement of material along the endosomal pathway; they also demonstrate a functional interaction between profilin and DdLIMP that may connect phosphoinositide-based signaling through the actin cytoskeleton with endolysosomal membrane trafficking events.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.11.6.2019