Biology subjects

Rabino, A. F.

Publications and source records attributed to Rabino, A. F..

3 recordsLinked to original sources

bioRxiv2026

SGEF coordinates epithelial morphogenesis by regulating junction stability, collective migration, and extracellular matrix remodeling

Polarized epithelia are essential for organ function, and disruption of epithelial polarity is a hallmark of many diseases, including cancer. We previously showed that the RhoG-specific guanine nucleotide exchange factor SGEF interacts with the Scribble polarity complex to regulate epithelial junction assembly in 2D monolayers. However, its role in epithelial morphogenesis and lumen formation in 3D remains unknown. Here, we combined quantitative morphometric analysis with long-term live-cell imaging to investigate the role of SGEF during MDCK cyst development. SGEF KD disrupted normal lumenogenesis, producing enlarged cysts with multiple collapsed lumens accompanied by reduced E-cadherin, {beta}-catenin, and ZO-1 expression. Loss of SGEF also altered the distribution of the actomyosin network. Re-expression of WT SGEF restored the normal phenotype, whereas restoration of E-cadherin and ZO-1 partially rescued lumen architecture, identifying the loss of junction integrity as a key driver of the morphogenetic defects. Unexpectedly, live-cell imaging revealed increased motility and frequent cyst fusion in SGEF-KD cysts. Restoring E-cadherin levels abolished cyst migration, while inhibition of matrix metalloproteinases markedly restored normal cyst volume and lumen architecture, identifying extracellular matrix remodeling as an additional contributor to the SGEF-deficient phenotype. Together, these findings identify SGEF as a key regulator of epithelial morphogenesis, coordinating junction integrity, actomyosin organization, lumen formation, and collective migration.

cell biology↗

bioRxiv2024

The Scribble/SGEF/Dlg1 complex regulates the stability of apical junctions in epithelial cells

SGEF, a RhoG specific GEF, can form a ternary complex with the Scribble polarity complex proteins Scribble and Dlg1, which regulates the formation and maintenance of adherens junctions and barrier function of epithelial cells. Notably, silencing SGEF results in a dramatic downregulation of the expression of both E-cadherin and ZO-1. However, the molecular mechanisms involved in the regulation of this pathway are not known. Here, we describe a novel signaling pathway governed by the Scribble/SGEF/Dlg1 complex. Our results show that an intact ternary complex is required to maintain the stability of the apical junctions, the expression of ZO-1, and TJ permeability. In contrast, only SGEF is necessary to regulate E-cadherin expression. The absence of SGEF destabilizes the E-cadherin/catenin complex at the membrane, triggering a positive feedback loop that exacerbates the phenotype through the repression of E-cadherin transcription in a process that involves the internalization of E-cadherin by endocytosis, {beta}-catenin signaling and the transcriptional repressor Slug.

cell biology↗

bioRxiv2022

ARHGAP17 regulates the spatiotemporal activity of Cdc42 at invadopodia

Invadopodia formation is regulated by Rho GTPases. However, the molecular mechanisms that control Rho GTPase signaling at invadopodia remain poorly understood. Here, we have identified ARHGAP17, a Cdc42-specific RhoGAP, as a key regulator of invadopodia in breast cancer cells and by RhoGAPs characterized a novel ARHGAP17-mediated signaling pathway that controls the spatiotemporal activity of Cdc42 during invadopodia turnover. Our results show that during invadopodia assembly, ARHGAP17 localizes to the invadopodia ring and restricts the activity of Cdc42 to the invadopodia core, where it promotes invadopodia growth. Invadopodia disassembly starts when ARHGAP17 translocates from the invadopodia ring to the core, in a process that is mediated by its interaction with the Cdc42 effector CIP4. Once at the core, ARHGAP17 inactivates Cdc42 to promote invadopodia disassembly. Our results in invadopodia provide new insights on the coordinated transition between the activation and inactivation of Rho GTPases.

cell biology↗