Dataset Information

DLG1 functions upstream of SDCCAG3 and IFT20 to control ciliary targeting of polycystin-2

ABSTRACT: Polarized vesicular trafficking directs specific receptors and ion channels to cilia, but the underlying mechanisms are poorly understood. Here we describe a role for DLG1, a core component of the Scribble polarity complex, in regulating ciliary protein trafficking in kidney epithelial cells. Conditional knockout of Dlg1 in mouse kidney caused causes ciliary elongation and cystogenesis, and cell-based proximity labelling proteomics and fluorescence microscopy showed alterations in the ciliary proteome upon loss of DLG1. Specifically, the retromer-associated protein SDCCAG3, IFT20 and polycystin-2 (PC2) were are reduced in cilia of DLG1 deficient cells compared to control cells. This phenotype was is recapitulated in vivo and rescuable by re-expression of wildtype DLG1, but not a Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)-associated DLG1 variant, p.T489R. Finally, biochemical approaches and Alpha Fold modelling suggested that SDCCAG3 and IFT20 form a complex that associates, at least indirectly, with DLG1. Our work identifies a key role for DLG1 in regulating ciliary protein composition and suggests that ciliary dysfunction of the p.T489R DLG1 variant may contribute to CAKUT.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast

DISEASE(S): Disease Free

SUBMITTER: Karsten Boldt

LAB HEAD: Dr. Karsten Boldt

PROVIDER: PXD051906 | Pride | 2025-05-07

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	JUN3659-S02-A-C1_cilia_BIOID2_WT_1.raw	Raw
	JUN3659-S03-A-C7_cilia_BIOID2_DLG1KO_1.raw	Raw
	JUN3659-S04-A-C25_DLG1_BIOID2_1.raw	Raw
	JUN3659-S05-A-C13_BIOID2_WT_1.raw	Raw
	JUN3659-S06-A-C19_BIOID2_DLG1KO_1.raw	Raw

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Publications

DLG1 functions upstream of SDCCAG3 and IFT20 to control ciliary targeting of polycystin-2.

Rezi Csenge K CK Aslanyan Mariam G MG Diwan Gaurav D GD Cheng Tao T Chamlali Mohamed M Junger Katrin K Anvarian Zeinab Z Lorentzen Esben E Pauly Kleo B KB Afshar-Bahadori Yasmin Y Fernandes Eduardo Fa EF Qian Feng F Tosi Sébastien S Christensen Søren T ST Pedersen Stine F SF Strømgaard Kristian K Russell Robert B RB Russell Robert B RB Miner Jeffrey H JH Mahjoub Moe R MR Boldt Karsten K Roepman Ronald R Pedersen Lotte B LB

EMBO reports 20240607 7

Polarized vesicular trafficking directs specific receptors and ion channels to cilia, but the underlying mechanisms are poorly understood. Here we describe a role for DLG1, a core component of the Scribble polarity complex, in regulating ciliary protein trafficking in kidney epithelial cells. Conditional knockout of Dlg1 in mouse kidney causes ciliary elongation and cystogenesis, and cell-based proximity labeling proteomics and fluorescence microscopy show alterations in the ciliary proteome upo ...[more]

PMID: 38849673

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