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Journal of cellular physiology
02, 2021;236 (2): 1270-1280.

Role of the small GTPase activating protein IQGAP1 in collagen phagocytosis.

Kei Nakajima, Pamela D Arora, Ajay Plaha, Christopher A McCulloch
Author Information
  1. Kei Nakajima: Department of Clinical Pathophysiology, Tokyo Dental College, Chiyoda-ku, Tokyo, Japan.
  2. Pamela D Arora: Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
  3. Ajay Plaha: Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
  4. Christopher A McCulloch: Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. ORCID
PMID: 32643295 DOI: 10.1002/jcp.29933

Abstract

Many adult connective tissues undergo continuous remodeling to maintain matrix homeostasis. Physiological remodeling involves the degradation of collagen fibers by the intracellular cathepsin-dependent phagocytic pathway. We considered that a multidomain, small GTPase activating protein, IQGAP1, which is involved in the generation of cell extensions, is required for collagen phagocytosis, possibly arising from its interactions with cdc42 and the actin-binding protein Flightless I (FliI). We examined the role of IQGAP1 in collagen phagocytosis by human gingival fibroblasts (HGFs) and by IQGAP1+/+ and IQGAP1-/- mouse embryonic fibroblasts. IQGAP1 was strongly expressed by HGFs, localized to vinculin-stained cell adhesions and sites where cell extensions are initiated, and colocalized with FliI. Immunoprecipitation showed that IQGAP1 associated with FliI. HGFs showed 10-fold increases of collagen binding, 6-fold higher internalization, and 3-fold higher β1 integrin activation between 30 and 180 min after incubation with collagen. Compared with IQGAP1+/+ fibroblasts, deletion of IQGAP1 reduced collagen binding (1.4-fold), collagen internalization (3-fold), β1 integrin activation (2-fold), and collagen degradation (1.8-fold). We conclude that IQGAP1 affects collagen remodeling through its regulation of phagocytic degradation pathways, which may involve the interaction of IQGAP1 with FliI.

Keywords

cell adhesion cell extensions collagen phagocytosis small GTPases

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Grants

  1. MOP-36322/CIHR

MeSH Term

Animals
Cell Adhesion
Collagen
Fibroblasts
Gingiva
Humans
Integrin beta1
Mice
Microfilament Proteins
Monomeric GTP-Binding Proteins
Phagocytosis
Protein Binding
Signal Transduction
Trans-Activators
cdc42 GTP-Binding Protein
ras GTPase-Activating Proteins

Chemicals

FLII protein, human
IQ motif containing GTPase activating protein 1
Integrin beta1
Microfilament Proteins
Trans-Activators
ras GTPase-Activating Proteins
Collagen
CDC42 protein, human
Monomeric GTP-Binding Proteins
cdc42 GTP-Binding Protein
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 2

Word Cloud

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