Biology subjects

de la Cruz, L.

Publications and source records attributed to de la Cruz, L..

3 recordsLinked to original sources

bioRxiv2026

Cholesterol, PtdIns(4,5)P2, and Actin Regulate BK Channel Nanoscale Organization

BK channels form nanoscale clusters, but the membrane and cytoskeletal mechanisms that organize these structures remain poorly understood. Using super-resolution imaging and FRAP, we dissect how cholesterol, PtdIns(4,5)P2, and actin govern BK channel organization expressed heterologously in tsA-201 cells and expressed endogenously in INS-1 cells. Cholesterol depletion produced opposite outcomes across these systems, enlarging clusters in heterologous cells but reducing both size and density in INS-1 cells. PtdIns(4,5)P2 displayed a biphasic regulatory profile: both enrichment and depletion enlarged clusters, revealing that BK assemblies are tuned to a narrow PtdIns(4,5)P2 set point. Actin disruption consistently reduced cluster size and density. Together, these findings show that cholesterol, PtdIns(4,5)P2, and actin are not only functional regulators of BK channels but also key determinants of their nanoscale organization. Across perturbations, changes in channel density strongly predicted changes in cluster size, identifying density as a central organizing principle. Significance statementThis study shows that the nanoscale organization of BK channels is dynamically controlled by membrane lipids and the cytoskeleton, demonstrating that ion channel organization is not fixed but actively shaped by the local membrane environment. Across perturbations, cluster size scales with channel density, underscoring density as a major driver of BK nanoscale organization.

biophysics↗

bioRxiv2025

Genomic connectivity and adaptation signals of the freshwater sponge Ephydatia muelleri across its distribution

1.Freshwater sponges fulfill critical ecological functions, including maintaining water quality, regulating nutrient dynamics, offering habitats for diverse taxa, and serving as a vital food source for various species. However, their patterns of dispersal and genetic connectivity remain inadequately understood, posing significant challenges to effective conservation assessments. We examined genetic connectivity and genetic adaptation to local environmental conditions in Ephydatia muelleri across its geographic range using ddRADseq-derived SNPs from 106 individuals collected from 11 localities spanning North America, Europe, and Asia. Analysis of 3,182 neutral SNPs revealed low connectivity and strong genetic structure among regions within two main genetic clusters of North America and Eurasia, while 115 SNPs identified to be under selection showed considerable evidence for differentiated, polygenic adaptation to light and temperature conditions across sampled locations, as well as selection on gene regulatory processes. These findings align with the "monopolization hypothesis", suggesting that historical climatic and geological conditions of the Last Glacial Maximum, including habitat expansion, contraction, and natural barriers, have contributed more to the current genetic structure of E. muelleri populations than contemporary gene flow, which is restricted by monopolistic habitat colonization by this species. Our results provide novel support for ecological theory on dispersal in aquatic invertebrates, as well as insights into the plasticity of E. muelleri in the face of varying environmental conditions that are fundamentally important for freshwater ecosystem conservation.

evolutionary biology↗

bioRxiv2023

Sympathetic Motor Neuron Dysfunction is a Missing Link in Age-Associated Sympathetic Overactivity

Overactivity of the sympathetic nervous system is a hallmark of aging. The cellular mechanisms behind this overactivity remain poorly understood, with most attention paid to likely central nervous system components. In this work, we hypothesized that aging also affects the function of motor neurons in the peripheral sympathetic ganglia. To test this hypothesis, we compared the electrophysiological responses and ion-channel activity of neurons isolated from the superior cervical ganglia of young (12 weeks), middle-aged (64 weeks), and old (115 weeks) mice. These approaches showed that aging does impact the intrinsic properties of sympathetic motor neurons, increasing spontaneous and evoked firing responses. A reduction of M current emerged as a major contributor to age-related hyperexcitability. Thus, it is essential to consider the effect of aging on motor components of the sympathetic reflex as a crucial part of the mechanism involved in sympathetic overactivity.

physiology↗