Role of the small GTPase activating protein IQGAP1 in collagen phagocytosis
Role of the small GTPase activating protein IQGAP1 in collagen phagocytosis
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小GTP酶激活蛋白IQGAP1在胶原吞噬作用中的作用
DOI：
10.1002/jcp.29933
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发表时间：
2021
影响因子：
5.6
通讯作者：
McCulloch Christopher A.
中科院分区：
文献类型：
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作者：
Nakajima Kei;Arora Pamela D.;Plaha Ajay;McCulloch Christopher A.
许多成人结缔组织经历持续的重塑以维持基质稳态。生理重塑涉及通过细胞内组织蛋白酶依赖性吞噬途径降解胶原纤维。我们认为，一个多结构域，小的GT3激活蛋白，IQGAP 1，这是参与细胞延伸的产生，是胶原蛋白吞噬作用所必需的，可能是由于它与cdc 42和肌动蛋白结合蛋白Flightless I（FliI）的相互作用。我们研究了IQGAP 1在人牙龈成纤维细胞（HGF）和IQGAP 1 +/+和IQGAP 1 −/−小鼠胚胎成纤维细胞的胶原吞噬作用中的作用。IQGAP 1由HGF强烈表达，定位于黏着斑蛋白染色的细胞粘附和细胞延伸起始部位，并与FliI共定位。免疫沉淀显示IQGAP 1与FliI结合。在与胶原蛋白孵育后30至180分钟，HGF显示胶原蛋白结合增加10倍，内化增加6倍，β1整合素活化增加3倍。与IQGAP 1 +/+成纤维细胞相比，IQGAP 1的缺失降低了胶原结合（1.4倍）、胶原内化（3倍）、β1整合素活化（2倍）和胶原降解（1.8倍）。我们的结论是，IQGAP 1影响胶原重塑通过其调节吞噬细胞降解途径，这可能涉及IQGAP 1与FliI的相互作用。
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.