Pericentrin, a centrosomal protein related to microcephalic primordial dwarfism, is required for olfactory cilia assembly in mice

Abstract

The Drosophila pericentrin-like protein has been shown to be essential for the formation of the sensory cilia of chemosensory and mechanosensory neurons by mutant analysis in flies, while the in vivo function of pericentrin, a well-studied mammalian centrosomal protein related to microcephalic primordial dwarfism, has been unclear. To determine whether pericentrin is required for ciliogenesis in mammals, we generated and analyzed mice with a hypomorphic mutation of Pcnt encoding the mouse pericentrin. Immunofluorescence analysis demonstrated that olfactory cilia of chemosensory neurons in the nasal olfactory epithelium were malformed in the homozygous mutant mice. On the other hand, the assembly of motile and primary cilia of non-neuronal epithelial cells and the formation of sperm flagella were not affected in the Pcnt-mutant mice. The defective assembly of olfactory cilia in the mutant was apparent from birth. The mutant animals displayed reduced olfactory performance in agreement with the compromised assembly of olfactory cilia. Our findings suggest that pericentrin is essential for the assembly of chemosensory cilia of olfactory receptor neurons, but it is not globally required for cilia formation in mammals.

Native Piezo2 Interactomics Identifies Pericentrin as a Novel Regulator of Piezo2 in Somatosensory Neurons

“…This is in accordance with our observations in primary DRG cultures (Supporting Fig. S-5) and previous reports in different cell types 25,27,41,46 . We did not observe any difference in Pcnt expression between Piezo2-GFP-positive (41.5 ± 0.06% of DRG were Piezo2-GFP-positive) and -negative neurons, respectively (Fig.…”

“…To this end we employed two different antibodies, which were extensively used in previous studies to visualize Pcnt [24][25][26][27][28][29] . In total agreement with these studies in different cell types both antibodies showed Pcnt expression at centrosomes and in puncta throughout the cytoplasm (Supporting Fig.…”

Promoter hijack reveals pericentrin functions in mitosis and the DNA damage response

“…4 Notably, ciliary abnormalities arose in the d-plp mutant flies, a phenotype reflected in the recent description of defective olfactory cilia formation in mice with a gene trap insertion in the 5' untranslated region of the first exon of Pcnt. 21 Together, these data clearly implicate pericentrin in regulatory and signaling functions of the centrosome. Loss-of-function mutations in PCNT have been described in microcephalic osteodysplastic primordial dwarfism type II (MOPD II; MIM 210720), a rare condition that is characterized by extremely short stature and microcephaly, but without marked mental retardation.…”

Meier-Gorlin syndrome mutations disrupt an Orc1 CDK inhibitory domain and cause centrosome reduplication

“…Patients have primordial dwarfism, microcephaly, and developmental abnormalities in the ear and patella (Klingseisen and Jackson 2011). Other developmental disorders that cause primordial dwarfism and microcephaly, including Seckel syndrome, have mutations in the centrosome proteins CPAP (CENP-J), PCNT, and CEP152, although defects in a few noncentrosome proteins such as ATM and IGF1 are also associated with microcephalic primordial dwarfism (Rauch et al 2008;Miyoshi et al 2009; Thornton and Woods 2009;Kitagawa et al 2011;Klingseisen and Jackson 2011;Sir et al 2011;Tang et al 2011). A survey of the mutations and phenotypes in 45 Meier-Gorlin syndrome patients demonstrated that compared with patients with mutations in Orc4, Cdc6, and Cdt1, all of the patients with mutations in Orc1 were of significantly shorter stature and had increased microcephaly and a significantly proportionally smaller head circumference and brain (de Munnik et al 2012).…”