Figure Fig. 4.

The expression of Nrg1 in granulosa cells during the ovulation process. a The gene construction of Nrg1. Nrg1 has three different transcription start sites. Type I Nrg1 is expressed from exon1, whereas type I Nrg1 mRNA lucks the exon encoding cysteine rich domain via the specific splicing dependent manner. Type II Nrg1 lucks the exons encoding Ig‐like domain and cysteine rich domain. Type III Nrg1 lucks Ig‐like domain, but has a cysteine‐rich domain. All of types of Nrg1 mRNA contain exons encoding EGF‐like domain, transmembrane domain, and signal sequence. b Type III Nrg1 is only induced in granulosa cells during the ovulation process. The specific primer sets to recognize each type of Nrg1 were used for RT‐PCR study. The data revealed that type III Nrg1 was expressed in mouse granulosa cells at 4 h after hCG injection. mRNA recovered from brain was used as positive control. c The construction of NRG1 and the image how to activate its receptor. Type III NRG1 that contains a signal sequence (black box), two transmembrane domains (green box and purple circle) and two protease targeting sequences (blue and red triangles) and a ligand domain (red box) forms a loop structure to present the ligand domain in the extracellular domain. Both proteases, ADAM19 (blue scissors) and MMP4 (brown scissors), are activated by hCG injection, which results in the release of the ligand domain of NRG1 to activate ErbB2/ErbB3 heterodimer