Blockade of FGFR1 Trafficking to the Cell Surface Results in the Partial Mistargeting of the Receptor to Peroxisomes.

Fibroblast growth factor receptor 1 (FGFR1) is a cell surface receptor tyrosine kinase implicated in cellular signaling and homeostasis. Several reports indicate that N-glycosylation of FGFR1 is critical for the FGFR1 trafficking to the cell surface, as glycosylation-deficient mutant of FGFR1 (FGFR1.GF) is trapped inside the cell, in the endoplasmic reticulum (ER), and in the nuclear envelope. Our recent mass spectrometry analyses revealed dehydrogenase/reductase 2 (DHRS2) as a putative binding partner of the intracellular FGFR1.GF. Here, we identified a peroxisomal targeting signal 1 (PTS1) at the C-terminus of DHRS2 and demonstrated that DHRS2 is dually targeted to peroxisomes and mitochondria. Furthermore, we determined that knockdown of DHRS2 results in increased number of peroxisomes, implicating the role of DHRS2 in peroxisome biogenesis. Using proximity ligation assay (PLA), we confirmed the interaction between FGFR1.GF and DHRS2 and demonstrated that FGFR1.GF/DHRS2 complexes are predominantly detected in peroxisomes. In agreement, we detected a small fraction of FGFR1.GF in peroxisomes. Taken together our data indicate that accumulation of FGFR1.GF in the ER may result in FGFR1.GF targeting to peroxisomes. Furthermore, we reveal interconnection between FGFR1 and DHRS2 and their role in peroxisome biogenesis.