Biology subjects

Jayathilake, A. L.

Publications and source records attributed to Jayathilake, A. L..

2 recordsLinked to original sources

bioRxiv2022

The microtubule minus end-binding protein CAMSAP2 does not regulate microtubule dynamics in primary pancreatic β-cells but facilitates insulin secretion

Glucose stimulation induces the remodeling of microtubules in Islet {beta}-cells to potentiate glucose-stimulated insulin secretion. CAMSAP2 is a microtubule minus-end binding protein and is reported to stabilize and position microtubules in several non-{beta}-cells, such as human retinal pigment epithelium cells. In immortalized insulinoma MIN6 cells, CAMSAP2 binds to and forms short stretches at microtubule minus ends in the cytoplasm, which is consistent with the reported subcellular localization and functions of CAMSAP2 in non-{beta}-cells. Surprisingly, we found that CAMSAP2 expressed in primary islet {beta}-cells does not form short stretches in the cytoplasm, but instead is localized to the Golgi apparatus. This novel localization is specific to {beta}-but not -cells in islets and it is independent of MT-binding. Knockdown of CAMSAP2 by shRNA impairs Golgi-ER trafficking, reduces total insulin content, and attenuates GSIS without affecting the MT dynamics or releasability of insulin granules in islet {beta}-cells. Corresponding to these results, we found that primary islets and MIN6 cells express different CAMSAP2 isoforms. We propose that primary islet {beta} cells use a novel CAMSAP2 isoform for a MT-independent non-canonical function, which is to promote Golgi-ER trafficking that supports efficient production of insulin secretory granules.

cell biology↗

bioRxiv2021

Weakly migratory metastatic breast cancer cells activate fibroblasts via microvesicle-Tg2 to facilitate dissemination and metastasis

Cancer cell migration is highly heterogeneous, and the migratory capability of cancer cells is thought to be an indicator of metastatic potential. It is becoming clear that a cancer cell does not have to be inherently migratory to metastasize, with weakly migratory cancer cells often found to be highly metastatic. However, the mechanism through which weakly migratory cells escape from the primary tumor remains unclear. Here, utilizing phenotypically sorted highly and weakly migratory breast cancer cells, we demonstrate that weakly migratory metastatic cells disseminate from the primary tumor via communication with stromal cells. While highly migratory cells are capable of single cell migration, weakly migratory cells rely on cell-cell signaling with fibroblasts to escape the primary tumor. Weakly migratory cells release microvesicles rich in tissue transglutaminase 2 (Tg2) which activate fibroblasts and lead weakly migratory cancer cell migration in vitro. These microvesicles also induce tumor stiffening and fibroblast activation in vivo and enhance the metastasis of weakly migratory cells. Our results identify microvesicles and Tg2 as potential therapeutic targets for metastasis and reveal a novel aspect of the metastatic cascade in which weakly migratory cells release microvesicles which activate fibroblasts to enhance cancer cell dissemination.

cancer biology↗