Epac1 interacts with importin ß1 and controls neurite outgrowth independently of cAMP and Rap1.
Sci Rep
; 6: 36370, 2016 11 03.
Article
in En
| MEDLINE
| ID: mdl-27808165
ABSTRACT
Exchange protein directly activated by cAMP-1 (Epac1) is a cAMP sensor that regulates multiple cellular functions including cellular migration, proliferation and differentiation. Classically, Epac1 is thought to exert its effects through binding of cAMP leading to a conformational change in Epac1 and its accumulation at the plasma membrane (PM) where it activates Rap1. In search for regulators of Epac1 activity, we show here that importin ß1 (impß1) is an Epac1 binding partner that prevents PM accumulation of Epac1. We demonstrate that in the absence of impß1, endogenous as well as overexpressed Epac1 accumulate at the PM. Moreover, agonist-induced PM translocation of Epac1 leads to dissociation of Epac1 from impß1. Localization of Epac1 at the PM in the absence of impß1, requires residue R82 in its DEP domain. Notably, the PM accumulation of Epac1 in the absence of impß1 does not require binding of cAMP to Epac1 and does not result in Rap1 activation. Functionally, PM accumulation of Epac1, an Epac1 mutant deficient in cAMP binding, or an Epac1 mutant tethered to the PM, is sufficient to inhibit neurite outgrowth. In conclusion, we uncover a cAMP-independent function of Epac1 at the PM and demonstrate that impß1 controls subcellular localization of Epac1.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Membrane
/
Guanine Nucleotide Exchange Factors
/
Beta Karyopherins
/
Neuronal Outgrowth
Limits:
Humans
Language:
En
Journal:
Sci Rep
Year:
2016
Document type:
Article
Affiliation country:
United States