Formin-like 1β phosphorylation at S1086 is necessary for secretory polarized traffic of exosomes at the immune synapse in Jurkat T lymphocytes.

We analyzed here how formin-like 1 β (FMNL1β), an actin cytoskeleton-regulatory protein, regulates microtubule-organizing center (MTOC) and multivesicular bodies (MVB) polarization and exosome secretion at an immune synapse (IS) model in a phosphorylation-dependent manner. IS formation was associated with transient recruitment of FMNL1β to the IS, which was independent of protein kinase C δ (PKCδ). Simultaneous RNA interference of all FMNL1 isoforms prevented MTOC/MVB polarization and exosome secretion, which were restored by FMNL1βWT expression.

EVC-EVC2 complex stability and ciliary targeting are regulated by modification with ubiquitin and SUMO.

Ellis van Creveld syndrome and Weyers acrofacial dysostosis are two rare genetic diseases affecting skeletal development. They are both ciliopathies, as they are due to malfunction of primary cilia, microtubule-based plasma membrane protrusions that function as cellular antennae and are required for Hedgehog signaling, a key pathway during skeletal morphogenesis. These ciliopathies are caused by mutations affecting the EVC-EVC2 complex, a transmembrane protein heterodimer that regulates Hedgehog signaling from inside primary cilia.

One master to rule them all.

Multiciliated cells rely on the same master regulator as dividing cells to amplify the number of centrioles needed to generate the hair-like structures that coat their cell surface.

Multiple ciliary localization signals control INPP5E ciliary targeting.

Primary cilia are sensory membrane protrusions whose dysfunction causes ciliopathies. INPP5E is a ciliary phosphoinositide phosphatase mutated in ciliopathies like Joubert syndrome. INPP5E regulates numerous ciliary functions, but how it accumulates in cilia remains poorly understood.

HTR6 and SSTR3 targeting to primary cilia.

Primary cilia are hair-like projections of the cell membrane supported by an inner microtubule scaffold, the axoneme, which polymerizes out of a membrane-docked centriole at the ciliary base. By working as specialized signaling compartments, primary cilia provide an optimal environment for many G protein-coupled receptors (GPCRs) and their effectors to efficiently transmit their signals to the rest of the cell. For this to occur, however, all necessary receptors and signal transducers must first accumulate at the ciliary membrane.

HTR6 and SSTR3 ciliary targeting relies on both IC3 loops and C-terminal tails.

G protein-coupled receptors (GPCRs) are the most common pharmacological target in human clinical practice. To perform their functions, many GPCRs must accumulate inside primary cilia, microtubule-based plasma membrane protrusions working as cellular antennae. Nevertheless, the molecular mechanisms underlying GPCR ciliary targeting remain poorly understood.

Prothymosin α interacts with SET, ANP32A and ANP32B and other cytoplasmic and mitochondrial proteins in proliferating cells.

Prothymosin α (ProTα) is an acidic protein with a nuclear role related to the chromatin activity through its interaction with histones in mammalian cells. ProTα acts as an anti-apoptotic factor involved in the control of the apoptosome activity in the cytoplasm, however the mechanisms underlying this function are still known. ProTα shares similar biological functions with acidic nuclear-cytoplasmic shuttling proteins included in SET and ANP32 family members.

The influence of phosphorylation of prothymosin α on its nuclear import and antiapoptotic activity.

Phosphorylation of prothymosin α (ProTα) appears not to affect its influence on chromatin remodelling. To determine whether it affects nuclear import or cytosolic antiapoptotic activity, cells were transfected with vectors generating tagged recombinant ProTα (rProTα), either wild-type (rProTα-wt), which is partially phosphorylated posttranslation or the nonphosphorylatable rProTα-T7A. Immunofluorescence microscopy showed the predominant location of native ProTα, rProTα-wt, and rProTα-T7A in the nucleus.

The M2-type isoenzyme of pyruvate kinase phosphorylates prothymosin α in proliferating lymphocytes.

Prothymosin α (ProTα) is a multifunctional protein that, in mammalian cells, is involved in nuclear metabolism through its interaction with histones and that also has a cytosolic role as an apoptotic inhibitor. ProTα is phosphorylated by a protein kinase (ProTαK), the activity of which is dependent on phosphorylation. ProTα phosphorylation also correlates with cell proliferation.