Human Disease Model Report: kidney disease (postulated), PALS1-related

General Information

Name

kidney disease (postulated), PALS1-related

FlyBase ID

FBhh0000833

Disease Ontology Term

kidney disease

Parent Disease

OMIM

Overview

Investigations using mice have implicated the MPP5 ortholog in the development of kidney disease; specifically, haploinsufficiency for the gene leads to formation of glomerular and tubular cysts. MPP5 encodes a member of the membrane-associated guanylate kinase (MAGUK) gene superfamily; it one of the components of the Crumbs (CRB) complex. There is a single orthologous gene in Drosophila, sdt, for which multiple genetic reagents, including classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis, have been generated.

The human PALS1 gene has not been introduced into flies.

The sdt-encoded protein is one of three proteins described as core components of the Drosophila Crumbs Complex (CRBC; see FBgg0001763). The CRBC plays a role in the establishment of apico-basal cell polarity in epithelial cells.

Animals homozygous for amorphic or loss-of-function alleles of Dmel\sdt die during the embryonic stage. Homozygous embryos derived from germ-line clones exhibit severe malformations and/or an absence of epidermis; they also exhibit abnormal zonula adherens formation. Nephrocyte-specific knockdown of sdt, effected by RNAi, results in reduced uptake efficiency of nephrocytes (based on an ANF-RFP filtration assay) and malformed slit-diaphragm-like structures.

[updated Apr. 2024 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: kidney disease (postulated), PALS1-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

MPP5 encodes a member of the p55-like subfamily of the membrane-associated guanylate kinase (MAGUK) gene superfamily. The MPP5 protein is one of the components of the Crumbs complex; it may play a role in tight junctions biogenesis and in the establishment of cell polarity in epithelial cells. [Gene Cards, MPP5; 2018.07.05]

(FlyBase Curators, 2013-)

In Drosophila, there are four proteins that can be classified as the core components of the Drosophila Crumbs complex: the products of the genes crb, sdt, Patj, and veli (Bulgakova and Knust, 2009; pubmed:19625503). These four meet the criteria of colocalization with, immunoprecipitation with, and direct interaction with other members of the complex in all of the cell types in which they are expressed.

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): PALS1
Gene Cards: MPP5 gene
Gene Cards: PALS1
MedlinePlus (gene): PALS1
MARRVEL (human gene): PALS1
NCBI (Entrez) gene: PALS1; protein associated with LIN7 1, MAGUK p55 family member

Disease synonyms

kidney disease (postulated), MPP5-related

Related Diseases

Related human health report(s)

kidney disease (fly models overview)

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

PALS1; protein associated with LIN7 1, MAGUK p55 family member

D. melanogaster ortholog (based on DIOPT)

Dmel\sdt

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\sdt

Gene Snapshot

stardust (sdt) encodes membrane-associated guanylate kinase (MAGUK) protein involved in the maintenance of apico-basal cell polarity and the organization of zonula adherens. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

CRBC
NTK

Comments on ortholog(s)

High-scoring ortholog of human MPP5 (1 Drosophila to 1 human). Dmel\sdt shares 39% identity and 53% similarity with the human gene.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (8 groups)

sdt

protein-protein

Interacting group

Assay

References

sdt - aPKC

anti bait coimmunoprecipitation, western blot

(Koch et al., 2016)

sdt - baz

anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot, pull down

(Koch et al., 2016, Sen et al., 2015, Krahn et al., 2010)

sdt - crb

anti bait coimmunoprecipitation, peptide massfingerprinting, western blot, pull down, autoradiography, anti tag coimmunoprecipitation, two hybrid, coimmunoprecipitation

(Koch et al., 2016, Sen et al., 2015, Pocha et al., 2011, Li et al., 2008, Kolsch et al., 2007, Kempkens et al., 2006, Bachmann et al., 2001, Hong et al., 2001)

sdt - didum

anti bait coimmunoprecipitation, peptide massfingerprinting, western blot

(Pocha et al., 2011)

sdt - neur

anti tag coimmunoprecipitation, anti tag western blot

(Perez-Mockus et al., 2017)

sdt - par-6

pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot, two hybrid, peptide massfingerprinting

(Koch et al., 2016, Neumüller et al., 2012, Kempkens et al., 2006, Wang et al., 2004)

sdt - Patj

two hybrid, anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, peptide massfingerprinting

(Koch et al., 2016, Sen et al., 2015, Pocha et al., 2011, Bulgakova et al., 2010, Bulgakova et al., 2008)

sdt - veli

two hybrid, anti bait coimmunoprecipitation, western blot, pull down, tag visualisation

(Bachmann et al., 2004)

Alleles Reported to Model Human Disease (Disease Ontology) (5 alleles)

sdt

Models Based on Experimental Evidence ( 3 )

Allele

Disease

Evidence

References

sdt^XN

model of cancer

CEA with Ras85D^V12.UAS

(Pagliarini and Xu, 2003)

sdt^HMS01652

model of kidney disease

CEA

(Weide et al., 2017)

sdt^NIG.15342R

model of kidney disease

CEA

(Weide et al., 2017)

Modifiers Based on Experimental Evidence ( 5 )

Allele

Disease

Interaction

References

sdt^XN

exacerbates tauopathy

modeled by Hsap\MAPT^UAS.cWa

(Feuillette et al., 2020)

sdt^EP1143

exacerbates tauopathy

modeled by Hsap\MAPT^UAS.cWa

(Feuillette et al., 2020)

sdt^HMS01652

model of kidney disease

is ameliorated by yki^GD11187

(Weide et al., 2017)

sdt^G1472

exacerbates tauopathy

modeled by Hsap\MAPT^UAS.cWa

(Feuillette et al., 2020)

sdt^NIG.15342R

model of kidney disease

is ameliorated by yki^GD11187

(Weide et al., 2017)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

w¹¹¹⁸; P{GD15292}v29844

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00851}attP2

sdt^HMS00953

P{TRiP.HMS00953}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00953}attP2/TM3, Sb¹

sdt^GL00193

P{TRiP.GL00193}

y¹ sc^* v¹ sev²¹; P{TRiP.GL00193}attP2

sdt^HMS01652

P{TRiP.HMS01652}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01652}attP40

y¹ v¹; P{TRiP.HMS01904}attP40/CyO

sdt^HMJ22057

P{TRiP.HMJ22057}

y¹ v¹; P{TRiP.HMJ22057}attP40/CyO

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

sdt^Δ3

loss of function allele

FLPase

sdt^Δ3-GFP

loss of function allele

CRISPR/Cas9

w¹¹¹⁸ TI{TI}sdt^Δ3-GFP

sdt^EP1143

P-element activity

sdt^7D