Expression of Drosophila matrix metalloproteinases in cultured cell lines alters neural and glial cell morphology

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F21%3A00542362" target="_blank" >RIV/60077344:_____/21:00542362 - isvavai.cz</a>

Result on the web

<a href="https://www.frontiersin.org/articles/10.3389/fcell.2021.610887/pdf" target="_blank" >https://www.frontiersin.org/articles/10.3389/fcell.2021.610887/pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fcell.2021.610887" target="_blank" >10.3389/fcell.2021.610887</a>

Result language

angličtina

Original language name

Expression of Drosophila matrix metalloproteinases in cultured cell lines alters neural and glial cell morphology

Original language description

Matrix metalloproteinases (MMPs) are zinc- and calcium- dependent endopeptidases that play pivotal roles in many biological processes. The expression of several MMPs in the central nervous system (CNS) have been shown to change in response to injury and various neurological/neurodegenerative disorders. While extracellular MMPs degrade the extracellular matrix (ECM) and regulate cell surface receptor signaling, the intracellular functions of MMPs or their roles in CNS disorders is unclear. Around 23 different MMPs are found in the human genome with overlapping function, making analysis of the intracellular role of human MMPs a daunting task. However, the fruit fly Drosophila melanogaster genome encodes only two MMPs: dMMP1 and dMMP2. To better understand the intracellular role of MMPs in the CNS, we expressed Green Fluorescent Protein (GFP)- tagged dMMPs in SH-SY5Y neuroblastoma cells and C6 glioblastoma cell lines. Lipofection of GFP-dMMPs in SH-SY5Y cells enhanced nuclear rupture and reduced cell viability (coupled with increased apoptosis) as compared to GFP alone. In non-liposomal transfection experiments, dMMP1 localizes to both the cytoplasm and the nucleus whereas dMMP2 had predominantly cytoplasmic localization in both neural and glial cell lines. Cytoplasmic localization demonstrated co-localization of dMMPs with cytoskeleton proteins which suggests a possible role of dMMPs in cell morphology. This was further supported by transient dMMP expression experiments that showed that dMMPs significantly increased neurite formation and length in neuronal cell lines. Inhibition of endogenous MMPs decreased neurite formation, length and βIII Tubulin protein levels in differentiated SH-SY5Y cells. Further, transient expression experiments showed similar changes in glial cell morphology, wherein dMMP expression increased glial process formation and process length. Interestingly, C6 cells expressing dMMPs had a glia-like appearance, suggesting MMPs may be involved in intracellular glial differentiation. Inhibition or suppression of endogenous MMPs in C6 cells increased process formation, increased process length, modulated GFAP protein expression, and induced distinct glial-like phenotypes. Taken together, our results strongly support the intracellular role that dMMPs can play in apoptosis, cytoskeleton remodeling, and cell differentiation. Our studies further reinforce the use of Drosophila MMPs to dissect out the precise mechanisms whereby they exert their intracellular roles in CNS disorders.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10601 - Cell biology

Project

<a href="/en/project/EF18_070%2F0008772" target="_blank" >EF18_070/0008772: An expanded view of energy homeostasis: neural integration of insulin and adipokinetic hormone signalling</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Cell and Developmental Biology

ISSN

2296-634X

e-ISSN

2296-634X

Volume of the periodical

9

Issue of the periodical within the volume

MAY 13

Country of publishing house

CH - SWITZERLAND

Number of pages

16

Pages from-to

610887

UT code for WoS article

000654994900001

EID of the result in the Scopus database

2-s2.0-85107063981