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Biology subjects

Di Pietro, S.

Publications and source records attributed to Di Pietro, S..

4 recordsLinked to original sources

Growing Minds, Integrating Senses: Neural and Computational Insights into Age-related Changes in Audio-Visual and Tactile-Visual Learning in Children

Multisensory processing and learning shape cognitive and language development, influencing how we perceive and interact with the world from an early age. While multisensory processes mature into adolescence, it remains poorly understood how age influences multisensory associative learning. This study investigated age-related effects on multisensory processing and learning during audio-visual and tactile-visual learning in 67 children (5.7-13 years) by integrating behavioural and neuroimaging data with computational methods. A reinforcement-learning drift diffusion model revealed that older children processed information faster and made more efficient decisions on multisensory associations. These age-related increases coincided with higher activity in brain regions associated with cognitive control, multisensory integration, and memory retrieval, specifically during audio-visual learning. Notably, the bilateral anterior insula exhibited heightened activation in response to lower reward prediction errors, indicative of increased sensitivity to negative feedback with development. Finally, reward prediction errors modulated activation in reward processing and cognitive control regions, with this modulation remaining modality-independent and largely stable across age. In conclusion, while children employ similar learning strategies, older children make decisions more efficiently and engage neural resources more strongly. Our findings reflect ongoing maturation of neural networks supporting multisensory learning in middle childhood, enabling more adaptive learning in later childhood. Highlights- faster information processing in older children during a multisensory learning task - increasing brain activation with age in visual, parietal, and frontal regions - reward prediction error processing are independent of age and modality - heightened response to negative reward prediction errors with increasing age

neuroscience↗

Identification of a RAB32-LRMDA-Commander membrane trafficking complex reveals the molecular mechanism of human oculocutaneous albinism type 7

Commander is an endosome associated sixteen protein assembly that associates with the sorting nexin 17 (SNX17) cargo adaptor to regulate cell surface recycling of internalised integral membrane proteins including integrins and lipoprotein receptors. Mutations in Commander are causative for Ritscher-Schinzel syndrome (RSS), a multiorgan developmental disease associated with a core triad of cerebellar-cardiac-craniofacial malformation. Here, using unbiased proteomics and computational modelling, we identify leucine rich melanocyte differentiation associated (LRMDA) as a novel Commander binding protein. Using recombinant protein reconstitution, we show that LRMDA simultaneously associates with Commander and active RAB32, and, by revealing that LRMDA and SNX17 share a common mechanism of Commander association, establish the mutually exclusive nature of RAB32-LRMDA-Commander and SNX17-Commander assemblies. From functional analysis in human melanocytes, we establish an essential role for RAB32-LRMDA-Commander in melanosome biogenesis and pigmentation and reveal a distinct functional role for SNX17-Commander in this organelle biogenesis pathway. We reveal how LRMDA mutations, causative for oculocutaneous albinism type 7 (OCA7), a hypopigmentation disorder accompanied by poor visual acuity, uncouple RAB32 and Commander binding thereby establishing the mechanistic basis of this disease. Our discovery and characterisation of this alternative Commander assembly establishes an unrecognised plasticity of Commander function within a highly complex organelle biogenesis pathway. This extends Commander function beyond the confines of SNX17-mediated cell surface recycling into RAB32-family mediated biogenesis of lysosome-related organelles and, potentially, other RAB32 regulated pathways including host-pathogen defence mechanisms. Our work also extends the breath of Commander pathway dysfunction for human disease.

cell biology↗

Endogenous Rab38 regulates LRRK2's membrane recruitment and substrate Rab phosphorylation in melanocytes

Point mutations in LRRK2 cause Parkinsons Disease and augment LRRK2s kinase activity. However, cellular pathways that enhance LRRK2 kinase function have not been identified. While overexpressed Rab29 draws LRRK2 to Golgi membranes to increase LRRK2 kinase activity, there is little evidence that endogenous Rab29 performs this function under physiological conditions. Here we identify Rab38 as a novel physiological regulator of LRRK2. In mouse melanocytes, which express high levels of Rab38, Rab32, and Rab29, knockdown of Rab38 but not Rab32 or Rab29 decreases phosphorylation of multiple LRRK2 substrates, including Rab10 and Rab12, by both exogenous and endogenous LRRK2. In B16-F10 mouse melanoma cells, Rab38 drives LRRK2 membrane association, and overexpressed kinase-active but not kinase-inactive LRRK2 shows striking pericentriolar recruitment, which is dependent on the presence of endogenous Rab38 but not Rab32 or Rab29. Deletion or mutation of LRRK2 at the Rab38 binding site in the N-terminal armadillo domain decreases LRRK2 membrane association, pericentriolar recruitment, and ability to phosphorylate Rab10. Consistently, overexpression of LRRK2350-550, a fragment that encompasses the Rab38 binding site, blocks endogenous LRRK2s phosphorylation of Thr73-Rab10. Finally, disruption of BLOC-3, the guanine nucleotide exchange factor for Rab38 and 32, inhibits Rab38s regulation of LRRK2. In sum, our data identify Rab38 as a physiologic regulator of LRRK2 function and lend support to a model in which LRRK2 plays a central role in Rab GTPase coordination of vesicular trafficking.

cell biology↗

Tracking crystallophore nucleating properties: setting-up a database for statistical analysis.

In this article, the principle of a database aimed at facilitating the understanding of the unique protein nucleating properties of the Crystallophore is presented. A first analysis allows us to compare the efficiency of Tb-Xo4 with the new Lu-Xo4 variant, featuring improved phasing properties. Then, the concept of subset-of-interest is introduced to reveal potential antagonistic/synergistic effects between Tb-Xo4 and physico-chemical parameters of the crystallisation kits such as pH. The overall approach may be of interest for any studies working on solutions dedicated to improve the nucleating step in protein crystallization. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/057596v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@351291org.highwire.dtl.DTLVardef@5620fcorg.highwire.dtl.DTLVardef@8fadb2org.highwire.dtl.DTLVardef@d4c208_HPS_FORMAT_FIGEXP M_FIG C_FIG SynopsisA database and associated representation tools are highlighted to understand nucleating properties of the crystallophore.

biochemistry↗