WDR90

WDR90 is an evolutionarily conserved microtubule-associated protein that localizes to the central core region of centrioles and is required for ciliogenesis (PMID:28781053). It is integrated into the microtubule wall along the centriole central core, where its depletion impairs the recruitment of inner scaffold components and produces centriole structural abnormalities, establishing WDR90 as a determinant of centriole integrity (PMID:32946374). Its centriolar recruitment is governed by CEP350 as part of a CEP350–FOP–WDR90 axis that secures centriole architecture (PMID:36315013). Independent of this centriolar role, WDR90 physically associates with NLRC4 (but not NLRP3 or AIM2), alters NLRC4 distribution, and acts upstream of caspase-1 and ASC to potentiate inflammasome activity and antibacterial defense (PMID:31276698).

1. 2017 High

   Established WDR90 as the human homolog of a centriolar central core protein and tied it to ciliogenesis, defining its core cellular compartment and function.

   Evidence Quantitative mass spectrometry on purified Chlamydomonas centrioles, super-resolution microscopy, and RNAi knockdown with ciliogenesis readout in human cells

   PMID:28781053

   Open questions at the time

   • Molecular mechanism by which WDR90 supports ciliogenesis not resolved
   • Direct microtubule-binding biochemistry not established at this stage
2. 2017 Medium

   Independent interactome-based prediction and vertebrate validation reinforced WDR90 as a basal body/centriolar satellite protein within ciliopathy pathways.

   Evidence Computational prediction from hu.MAP protein complex map with in vivo zebrafish validation

   PMID:28596423

   Open questions at the time

   • Derived from large-scale interactome with limited WDR90-specific mechanism
   • Specific complex partners not defined
3. 2019 Medium

   Identified a non-centriolar role: WDR90 as a selective NLRC4 inflammasome component acting upstream of caspase-1, expanding its functional scope into innate immunity.

   Evidence Co-IP in HEK293 reconstitution, zebrafish overexpression with caspase-1 activity and Salmonella infection survival assays, and epistasis placing wdr90 upstream of Caspa and Asc

   PMID:31276698

   Open questions at the time

   • Single lab; reciprocal validation of the NLRC4 interaction in human cells limited
   • Relationship between centriolar and inflammasome functions unknown
   • Direct binding interface with NLRC4 not mapped
4. 2020 High

   Resolved where WDR90 sits at nanoscale and what it does there—mapping it to the centriole microtubule wall and showing it is required for inner scaffold component localization and structural integrity.

   Evidence Ultrastructure expansion microscopy (U-ExM) with WDR90 depletion and structural phenotype readout in human cells

   PMID:32946374

   Open questions at the time

   • Direct biochemical interactions with inner scaffold proteins not defined
   • Whether WDR90 binds microtubules directly versus via partners not resolved
5. 2022 Medium

   Placed WDR90 in an ordered recruitment pathway, showing CEP350 controls its centriolar localization via a CEP350-FOP-WDR90 axis.

   Evidence CEP350 knockout with immunofluorescence readout of WDR90 localization and epistasis analysis

   PMID:36315013

   Open questions at the time

   • Single lab
   • Direct versus indirect dependency on FOP not biochemically dissected
   • Molecular nature of the CEP350-WDR90 connection unknown

• How WDR90's centriolar scaffold function relates to its NLRC4 inflammasome role, and whether these reflect distinct pools or a shared mechanism, remains unresolved.
• No mechanistic link between centriole and inflammasome functions
• No structural model of WDR90 in either context
• Direct microtubule- and partner-binding biochemistry not established