ARHGAP21 prevents abnormal insulin release through actin rearrangement in pancreatic islets from neonatal mice.
OBJECTIVE
ARHGAP21 is a Rho GTPase-activating protein (RhoGAP) that associates with many proteins and modulates several cellular functions, including actin cytoskeleton rearrangement in different tissues. However, it is unknown whether ARHGAP21 is expressed in pancreatic beta cells and its function in these cells. Herein, we assess the participation of ARHGAP21 in insulin secretion.


METHODS
Neonatal mice were treated with anti-sense oligonucleotide against ARHG AP21 (AS) for 2 days, resulting in a reduction of the protein's expression of about 60% in the islets. F-actin depolimerization, insulin secretion,mRNA level of genes involved in insulin secretion, maturation and proliferation were evaluated in islets from both control and AS-treated mice.


RESULTS
ARHGAP21 co-localized with actin inMIN6 beta cells and with insulin in neonatal pancreatic islets. F-actin was reduced in AS-islets, as judged by lower phalloidin intensity. Insulin secretion was increased in islets from AS-treated mice, however no differences were observed in the GSIS (glucose-stimulated insulin secretion). In these islets, the pERK1/2 was increased, as well as the gene expressions of VAMP2 and SNAP25, proteins that are present in the secretory machinery. Maturation and cell proliferation were not affected in islets from AS-treated mice.


CONCLUSIONS
In conclusion, our data show, for the first time, that ARHGAP21 is expressed and participates in the secretory process of pancreatic beta cells. Its effect is probably via pERK1/2, which modulates the rearrangement of the cytoskeleton. ARHGAP21 also controls the expression of genes that encodes proteins of the secretory machinery.
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Sandra Mara
SM
Ferreira
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Gustavo Jorge
GJ
Santos
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Luiz F
LF
Rezende
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Luciana Mateus
LM
Gonçalves
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Junia Carolina
JC
Santos-Silva
Department of Internal Medicine, School of Medical Science, Hematology and Hemotherapy Center - Hemocentro, INCT Sangue, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Carolina Louzão
CL
Bigarella
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Everardo Magalhães
EM
Carneiro
Department of Internal Medicine, School of Medical Science, Hematology and Hemotherapy Center - Hemocentro, INCT Sangue, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Sara Teresinha Ollala
ST
Saad
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Antonio Carlos
AC
Boschero
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil. Electronic address: bsampaio@unicamp.br.
Helena Cristina
HC
Barbosa-Sampaio
D000199:Actins / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice
C459590:ARHGAP21 protein, human; D000199:Actins; D020690:GTPase-Activating Proteins; D007328:Insulin; D004247:DNA
ARHGAP21; Actin rearrangement; Glucose; Insulin secretion