The scaffolding protein IQGAP1 co-localizes with actin at the cytoplasmic face of the nuclear envelope: implications for cytoskeletal regulation

Abstract

IQGAP1 is an important cytoskeletal regulator, known to act at the plasma membrane to bundle and cap actin filaments, and to tether the cortical actin meshwork to microtubules via plus-end binding proteins. Here we describe the novel subcellular localization of IQGAP1 at the cytoplasmic face of the nuclear envelope, where it co-located with F-actin. The IQGAP1 and F-actin staining overlapped that of microtubules at the nuclear envelope, revealing a pattern strikingly similar to that observed at the plasma membrane. In detergent-extracted cells IQGAP1 was retained at cytoskeletal structures at the nuclear envelope. This finding has new implications for involvement of IQGAP1 in cell polarization and migration events and potentially in cell cycle-associated nuclear envelope assembly/disassembly.

IQGAP1 is associated with nuclear envelope reformation and completion of abscission

“…Depletion of IQGAP1 results in additional time spent in the abscission phase, failure to complete cytokinesis, and disrupted nuclear envelope staining of Nup98 as well as proteins containing FXFG repeat sequences during abscission. Consistent with this idea, IQGAP1 co-localizes with actin at the cytoplasmic face of the nuclear envelope, 36 where it is suggested to aid in maintaining the structural architecture of the nuclear envelope via a scaffolding function. 37 Our observations that nuclear envelope staining of these nucleoporins was not perturbed in interphase cells depleted of IQGAP1, when the nuclear envelope is established, indicate that IQGAP1 is required for NPC reassembly.…”

“…36 Here, it co-localizes with actin and is proposed to aid in maintaining structural architecture of the nuclear envelope via a scaffolding function. Consistent with this idea, the IQGAP1 partner, adenomatous polyposis coli (APC), binds Nup153 to promote anchorage of microtubules to the nuclear envelope.…”

IQGAP1: Insights into the function of a molecular puppeteer

“…MTOC reorientation is independent of Cdc42-induced changes in actin and microtubule stabilization in a dynein-dependent manner (Palazzo et al , 2001). IQGAP1 has also been found localized to the cytoplasmic face of the nuclear envelope, potentially promoting cell cycle-associated assembly and nuclear envelope disruption (Johnson and Henderson, 2012) (Figure 5B). …”

Alterations in gene expression induced by oxaliplatin based chemotherapy in colorectal cancer

“…All these findings point to a key role for IQGAP1 in the modulation of functions such as cell growth and survival, cell migration, and cytokinesis. Furthermore, some tumour cells exhibited a co-expression of IQGAP1 and β-tubulin in the nuclear envelope (NE) (Article 1, Fig.4 arrowheads), a co-localization that had already been described by Johnson et al [151] in several epithelial cancer cell lines. The authors correlated these data with a possible role for IQGAP1 in cell polarization and migration processes and in cell-cycle-associated NE assembly/disassembly, suggesting that the interplay between IQGAP1 and the microtubules (MT) may tether MT network to perinuclear actin to modulate the microtubule organizing centre (MTOC) and nuclear positioning during cell migration, a crucial process in carcinogenesis.…”

“…Notch signaling has a crucial role in the normal maintenance and homeostasis of the intestinal epithelium [59,60], regulating the balance between cell differentiation, proliferation and apoptosis and controlling the cellular fate of intestinal SCs and the differentiation of Goblet cells [61,62]. In many human cancers, including CRCs, abnormally activated Notch pathway was correlated with increased progression, metastatic potential and relapse [63][64][65].…”