Septin-microtubule association via a motif unique to isoform 1 of septin 9 tunes stress fibers.

Septins, a family of GTP-binding proteins that assemble into higher order structures, interface with the membrane, actin filaments and microtubules, and are thus important regulators of cytoarchitecture. Septin 9 (SEPT9), which is frequently overexpressed in tumors and mutated in hereditary neuralgic amyotrophy (HNA), mediates the binding of septins to microtubules, but the molecular determinants of this interaction remained uncertain. We demonstrate that a short microtubule-associated protein (MAP)-like motif unique to SEPT9 isoform 1 (SEPT9_i1) drives septin octamer-microtubule interaction in cells and in vitro reconstitutions.

iASPP contributes to cell cortex rigidity, mitotic cell rounding, and spindle positioning.

iASPP is a protein mostly known as an inhibitor of p53 pro-apoptotic activity and a predicted regulatory subunit of the PP1 phosphatase, which is often overexpressed in tumors. We report that iASPP associates with the microtubule plus-end binding protein EB1, a central regulator of microtubule dynamics, via an SxIP motif. iASPP silencing or mutation of the SxIP motif led to defective microtubule capture at the cortex of mitotic cells, leading to abnormal positioning of the mitotic spindle.

A proximity-labeling proteomic approach to investigate invadopodia molecular landscape in breast cancer cells.

Metastatic progression is the leading cause of mortality in breast cancer. Invasive tumor cells develop invadopodia to travel through basement membranes and the interstitial matrix. Substantial efforts have been made to characterize invadopodia molecular composition.

EB1-binding-myomegalin protein complex promotes centrosomal microtubules functions.

Control of microtubule dynamics underlies several fundamental processes such as cell polarity, cell division, and cell motility. To gain insights into the mechanisms that control microtubule dynamics during cell motility, we investigated the interactome of the microtubule plus-end-binding protein end-binding 1 (EB1). Via molecular mapping and cross-linking mass spectrometry we identified and characterized a large complex associating a specific isoform of myomegalin termed "SMYLE" (for short myomegalin-like EB1 binding protein), the PKA scaffolding protein AKAP9, and the pericentrosomal protein CDK5RAP2.

Memo is a copper-dependent redox protein with an essential role in migration and metastasis.

Memo is an evolutionarily conserved protein with a critical role in cell motility. We found that Memo was required for migration and invasion of breast cancer cells in vitro and spontaneous lung metastasis from breast cancer cell xenografts in vivo. Biochemical assays revealed that Memo is a copper-dependent redox enzyme that promoted a more oxidized intracellular milieu and stimulated the production of reactive oxygen species (ROS) in cellular structures involved in migration.

MEMO associated with an ErbB2 receptor phosphopeptide reveals a new phosphotyrosine motif.

Tyrosine phosphorylations are essential in signal transduction. Recently, a new type of phosphotyrosine binding protein, MEMO (Mediator of ErbB2-driven cell motility), has been reported to bind specifically to an ErbB2-derived phosphorylated peptide encompassing Tyr-1227 (PYD). Structural and functional analyses of variants of this peptide revealed the minimum sequence required for MEMO recognition.

ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells.

Microtubules (MTs) contribute to key processes during cell motility, including the regulation of focal adhesion turnover and the establishment and maintenance of cell orientation. It was previously demonstrated that the ErbB2 receptor tyrosine kinase regulated MT outgrowth to the cell cortex via a complex including Memo, the GTPase RhoA, and the formin mDia1. But the mechanism that linked this signaling module to MTs remained undefined.

LIFR beta plays a major role in neuronal identity determination and glial differentiation in the mouse facial nucleus.

In the hindbrain, generation of the facial nucleus involves complex developmental processes that will lead to the formation of a structure composed of motor neurons, astrocytes and oligodendrocytes. The implication of LIF-related cytokines in the development of this nucleus came to light with the analysis of mice mutant for the receptor of these cytokines, LIFR beta, which exhibit a massive loss of facial branchiomotor (fbm) neurons at birth and a severe decrease in GFAP expression, a marker of astrocytes. To uncover the cellular mechanisms regulated by LIFR beta during facial nucleus development, we first analyzed its expression pattern in the hindbrain.

Identification of lynx2, a novel member of the ly-6/neurotoxin superfamily, expressed in neuronal subpopulations during mouse development.

We isolated a new gene which shares all the features of the Ly-6/neurotoxin superfamily, from gene organization to predicted 3D structure. As it is preferentially expressed in the nervous system, we called this gene lynx2, by analogy with lynx1, a nAChR modulator. In embryonic and postnatal mouse, lynx2 is expressed in postmitotic central and peripheral neurons.

Fas/tumor necrosis factor receptor death signaling is required for axotomy-induced death of motoneurons in vivo.

Activation of the Fas death receptor leads to the death of motoneurons in culture. To investigate the role of Fas in programmed cell death and pathological situations, we used several mutant mice deficient for Fas signaling and made a novel transgenic FADD-DN (FAS-associated death domain-dominant-negative) strain. In vitro, motoneurons from all of these mice were found to be resistant to Fas activation and to show a delay in trophic deprivation-induced death.