Regulation of de- and reciliation by KRAS during muscle cell differentiation

aPKC exclusion from the apical cortex in enteroblasts maintains stem cell homeostasis in Drosophila.

Proper control of stem cell behavior is crucial for maintaining tissue homeostasis. In the Drosophila midgut, smooth septate junction (sSJ)-associated proteins play a crucial role in regulating intestinal stem cell (ISC) proliferation via atypical PKC (aPKC) activity. Here, we investigate the underlying mechanism. We found that aPKC in the apical cortex diminishes during enteroblast differentiation, in accordance with the apical accumulation of sSJ proteins. In sSJ protein-deficient conditions, aPKC remained in the apical cortex in enteroblasts, accompanied by ISC overproliferation. Manipulation of Kibra, an activator of the Hippo pathway with aPKC-binding properties, affected sSJ proteins depletion-induced ISC overproliferation in an aPKC-binding domain-dependent manner, revealing a link between aPKC and the Hippo- and/or Misshapen-Yorkie pathway in ISC proliferation. This study provides novel insights into the mechanism underlying stem cell regulation, in which an antagonistic interaction between aPKC and junctional proteins in differentiating progenitors is involved.

Soft matrix promotes ciliogenesis in human retinal pigment epithelial cells

The primary cilium (PC) is a microtubule-based mechanosensory organelle involved in signal transduction. Although the signaling functions of PC have been well studied, its interaction with the cell´s mechanical environment remains unclear. Here, we used polyacrylamide hydrogels to investigate how extracellular matrix (ECM) stiffness influences ciliogenesis in human retinal pigment epithelial (RPE1) cells. We found that a soft hydrogel (1 kPa) induces cilia formation and elongation in RPE1 cells independent of serum starvation, a classical in vitro method to promote ciliogenesis. Transcriptome analysis of serum-fed RPE1 cells on soft matrix revealed cell cycle exit and alterations in ECM and cytoskeletal gene expression that favor ciliogenesis. Moreover, we observed that despite being very long, cilia formed on a soft substrate are functional, as they transduce Sonic hedgehog signal normally. Transcriptome and microscopy analysis of two cilia-inducing conditions (soft substrate and serum starvation) revealed upregulation of cilia-related genes and downregulation of proliferation markers on both conditions. Autophagy genes were more enriched in serum-starved cells, whereas upregulation of ECM genes and downregulation of actin-related genes were more pronounced on soft matrix. Our study demonstrates that PC biogenesis can be mechanically induced in RPE1 cells on soft substrates independent of external biochemical cues.

COP9 complex maintains neuroblast growth and proliferation by regulating Akt/mTor pathway

establishes a CAV1-enriched microdomain at the ciliary transition zone to promote Sonic hedgehog signalling

Role of the primary cilium in muscle tissue.

Muscles are contractile tissues commonly classified into skeletal, cardiac, and smooth muscle. Each type exhibits distinct structural and functional properties that rely on coordinated signaling pathways to maintain homeostasis and adapt to physiological demands. The primary cilium is a solitary, microtubule-based organelle that protrudes from the cell surface and functions as a sensory platform for mechanical and chemical cues. Growing evidence has implicated primary cilia in the regulation of muscle biology. In skeletal muscle, primary cilia are present in quiescent satellite cells, where they contribute to the regulation of activation, self-renewal, and hypertrophic responses through signaling pathways such as Hedgehog and Wnt. In cardiac tissue, primary cilia have been identified in cardiac fibroblasts and developmental cardiac cell populations, where they have been associated fibrogenic responses, cardiac remodeling, and developmental signaling pathways. Similarly, in smooth muscle cells, primary cilia participate in mechanosensory signaling and have been implicated in the regulation of proliferative and migratory responses, particularly in vascular pathology. Alterations in ciliary structure or signaling components have been associated with impaired muscle regeneration, increased adipogenesis, and maladaptive tissue remodeling. This review examines the current evidence regarding the role of primary cilium in skeletal, cardiac, and smooth muscle and discusses its potential relevance in muscle disease, providing an integrated overview of cilium-dependent signaling across muscle tissues.

Rho/ROCK-dependent actomyosin contractility drives extracellular vesicle release from the cilium

The release of extracellular vesicles (EV) from the primary cilium is a conserved process observed in many cell types. It serves as a rapid and efficient mechanism to release select proteins from the cilium, which can be used for either intercellular communication or membrane material disposal. Previous studies have shown that the release of EVs from the cilium relies on the actin cytoskeleton and proposed several molecular mechanisms that may perform this function. Using the model of IMCD3 cells, we now demonstrate that this process relies on actomyosin contractility supported by non-muscle myosin IIA acting downstream of the RhoA-ROCK signaling pathway. We further showed that the cilia of these cells release EVs independently of de novo actin polymerization, which we confirmed using an in vivo model of mutant photoreceptor cells that release massive amounts of vesicles from their cilia instead of elaborating into light-sensitive outer segment membrane structures.