wsc1

UniProt ID: P87179
Organism: Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Review Status: DRAFT
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Gene Description

Wsc1 is a single-pass transmembrane mechanosensor in fission yeast that detects mechanical stress at the cell surface and coordinates cell wall repair with polar growth. Its extracellular WSC domain binds cell wall polysaccharides and forms force-dependent clusters at sites of wall compression. Clustering reduces lateral diffusion and is autonomous, independent of polarity machinery or downstream signaling. Through its cytoplasmic tail, Wsc1 recruits the Rho-GEF Rgf2p, which activates Rho1p to stimulate beta-1,3-glucan synthase for wall biosynthesis. Unlike S. cerevisiae Wsc1, the S. pombe Wsc1 signals independently of the MAPK cell integrity pathway. Wsc1 is concentrated at growing cell tips and is functionally redundant with Mtl2 for Rho1 activation, as wsc1-delta mtl2-delta double mutants are lethal.

Existing Annotations Review

GO Term Evidence Action Reason
GO:1903338 regulation of cell wall organization or biogenesis
IBA
GO_REF:0000033
ACCEPT
Summary: This phylogenetic inference is well-supported by direct experimental evidence in S. pombe. Wsc1 regulates cell wall organization through Rho1-mediated activation of glucan synthase, and wsc1-delta mutants show defective cell wall thickness homeostasis. The IBA annotation duplicates the experimentally supported EXP annotation but is independently correct.
GO:0016020 membrane
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: This IEA annotation is correct but overly general. Wsc1 is a single-pass transmembrane protein localized to the plasma membrane. More specific localization terms (plasma membrane, plasma membrane of cell tip) are annotated with experimental evidence.
GO:0005886 plasma membrane
IDA
PMID:23907979
The fission yeast cell wall stress sensor-like proteins Mtl2...
ACCEPT
Summary: Well-supported by GFP-tagged Wsc1 localization in Cruz et al. 2013. Wsc1p-GFP was observed at the cell periphery concentrated at cell tips, confirming plasma membrane localization.
Supporting Evidence:
PMID:23907979
Wsc1p-GFP was concentrated in patches at the cell tips
GO:0005886 plasma membrane
IDA
PMID:34666001
Detection of surface forces by the cell-wall mechanosensor W...
ACCEPT
Summary: Neeli-Venkata et al. 2021 extensively studied Wsc1-GFP dynamics at the plasma membrane, demonstrating force-dependent clustering at the cell surface. Confirms plasma membrane localization with detailed biophysical characterization.
Supporting Evidence:
PMID:34666001
we uncovered the formation of micrometer-sized clusters at sites of force application onto the CW
GO:0031520 plasma membrane of cell tip
IDA
PMID:23907979
The fission yeast cell wall stress sensor-like proteins Mtl2...
ACCEPT
Summary: Cruz et al. 2013 showed Wsc1p-GFP concentrated in patches specifically at cell tips, which is the site of polarized growth in fission yeast. This specific localization is functionally significant because it positions the mechanosensor where wall expansion and remodeling are most active. The falcon deep research corroborates this and notes the review-level extension that Wsc1 also localizes to the division septum, consistent with a role in cytokinesis-associated wall remodeling; cell-tip patch localization remains the primary experimentally supported pattern.
Supporting Evidence:
PMID:23907979
Wsc1p-GFP was concentrated in patches at the cell tips
file:SCHPO/wsc1/wsc1-deep-research-falcon.md
Wsc1 localizes at active growth sites and the division septum
GO:0140897 mechanoreceptor activity
EXP
PMID:34666001
Detection of surface forces by the cell-wall mechanosensor W...
ACCEPT
Summary: This is the core molecular function annotation for Wsc1. Neeli-Venkata et al. 2021 provided direct biophysical evidence that Wsc1 detects mechanical forces by forming dose-dependent clusters at sites of cell wall compression, with disassembly upon relaxation. The WSC domain binds cell wall polysaccharides and reduces lateral diffusivity under stress, functioning as an autonomous mechanosensing module. The falcon deep research corroborates the mechanosensor framing, describing Wsc1 as a plasma membrane-associated, serine-rich cell wall mechanosensor at active growth sites that detects mechanical stress during growth and wall remodeling.
Supporting Evidence:
PMID:34666001
Clusters assembled within minutes of CW compression, in dose dependence with mechanical stress and disassembled upon relaxation
PMID:34666001
Wsc1 may represent an autonomous module to detect and transduce local surface forces onto the CW
file:SCHPO/wsc1/wsc1-deep-research-bioreason-sft.md
A single-pass plasma membrane receptor in fission yeast that uses an extracellular carbohydrate-binding module to sense mechanical strain at growth sites
file:SCHPO/wsc1/wsc1-deep-research-falcon.md
plasma membrane-associated, serine-rich cell wall β€œmechanosensor”**, localized at active growth sites and the division septum, proposed to detect mechanical stress associated with growth and wall remodeling
GO:0050982 detection of mechanical stimulus
EXP
PMID:34666001
Detection of surface forces by the cell-wall mechanosensor W...
ACCEPT
Summary: Well-supported by Neeli-Venkata et al. 2021 who demonstrated that Wsc1 detects mechanical forces applied to the cell wall. Wsc1 clusters form at sites of compression within minutes and scale with the magnitude of applied force. This is a core biological process directly linked to the mechanoreceptor molecular function.
Supporting Evidence:
PMID:34666001
Clusters assembled within minutes of CW compression, in dose dependence with mechanical stress and disassembled upon relaxation
GO:1903338 regulation of cell wall organization or biogenesis
EXP
PMID:29689193
Mechanosensation Dynamically Coordinates Polar Growth and Ce...
ACCEPT
Summary: Davi et al. 2018 demonstrated that mechanosensing through the CWI pathway mediates a feedback loop controlling cell wall thickness homeostasis. wsc1-delta mutants were defective in this thickness homeostasis and lysed by wall rupture. This establishes Wsc1 as essential for regulating cell wall assembly in coordination with growth. The falcon deep research independently places Wsc1 upstream of Rho1 activation, with wsc1-delta cells showing reduced Rho1-GTP under cell wall stress and Wsc1 overexpression activating cell wall biosynthesis.
Supporting Evidence:
PMID:29689193
This feedback was mediated by mechanosensing through the CW integrity pathway, which probes strain in the wall to adjust synthase localization and activity to surface growth
PMID:29689193
Mutants defective in thickness homeostasis lysed by rupturing the wall
file:SCHPO/wsc1/wsc1-deep-research-falcon.md
Wsc1 acts upstream of Rho1
GO:0005886 plasma membrane
IDA
PMID:21832151
Endocytosis is essential for dynamic translocation of a synt...
ACCEPT
Summary: Kashiwazaki et al. 2011 is a study of syntaxin Psy1 relocalization during meiosis. Wsc1 (SPBC30B4.01c) appears in Table 3 as one of many plasma membrane proteins surveyed for localization during meiosis. Wsc1 was confirmed at the plasma membrane during vegetative growth using GFP-tagging. This is secondary data confirming PM localization.
Supporting Evidence:
PMID:21832151
SPBC30B4.01cwsc1+Transmembrane receptor1PMZK373
GO:0007166 cell surface receptor signaling pathway
IC
GO_REF:0000111
ACCEPT
Summary: This IC annotation infers involvement in cell surface receptor signaling pathway based on sequence similarity evidence for signal transduction receptor activity (GO:0004888). The inference is reasonable given that Wsc1 is a transmembrane receptor that signals through Rgf2/Rho1 to activate glucan synthase. However, the specific downstream pathway in S. pombe differs from the canonical CWI MAPK pathway seen in S. cerevisiae. The falcon deep research independently confirms the Wsc1 -> Rgf2 -> Rho1 axis and emphasizes that Pmk1/CIP MAPK activation persists in wsc1-delta, so this cell-surface receptor signaling is Rho1-directed rather than an essential upstream trigger of the Pmk1 cascade.
Supporting Evidence:
PMID:23907979
signaling from Wsc1p and Rgf2p through Rho1p to activate glucan synthase (GS)
file:SCHPO/wsc1/wsc1-deep-research-falcon.md
Wsc1 **interacts with the Rho-GEF Rgf2**, and **Wsc1 overexpression activates cell wall biosynthesis**, consistent with a Wsc1 β†’ Rgf2 β†’ Rho1 axis
file:SCHPO/wsc1/wsc1-deep-research-falcon.md
Pmk1 phosphorylation/activation is not markedly affected
GO:0035556 intracellular signal transduction
ISO
GO_REF:0000024
KEEP AS NON CORE
Summary: This ISO annotation transfers from S. cerevisiae Slg1/Wsc1 (SGD:S000005534). While S. pombe Wsc1 does participate in intracellular signal transduction through the Rgf2->Rho1->GS pathway, this term is quite broad. The specific signaling mechanism in S. pombe differs from S. cerevisiae (no MAPK pathway involvement). Acceptable as a general annotation. The falcon deep research reinforces that the S. pombe sensor-to-MAPK wiring differs from budding yeast, with Wsc1 acting upstream of Rho1 while Pmk1/CIP activation persists independently in its absence.
Supporting Evidence:
PMID:23907979
signaling from Wsc1p and Rgf2p through Rho1p to activate glucan synthase (GS)
file:SCHPO/wsc1/wsc1-deep-research-falcon.md
Wsc1 acts upstream of Rho1

Core Functions

Mechanosensing at the cell surface through force-dependent clustering mediated by WSC domain binding to cell wall polysaccharides, detecting mechanical strain during polar growth and stress

Supporting Evidence:
  • PMID:34666001
    Wsc1 accumulates to sites of enhanced mechanical stress through reduced lateral diffusivity, mediated by the binding of its extracellular WSC domain to CW polysaccharides
  • PMID:29689193
    This feedback was mediated by mechanosensing through the CW integrity pathway, which probes strain in the wall to adjust synthase localization and activity to surface growth

Activation of Rho1 GTPase through recruitment of the Rho-GEF Rgf2, coupling mechanosensing to beta-1,3-glucan synthase activation for cell wall biosynthesis and repair

Supporting Evidence:
  • PMID:23907979
    signaling from Wsc1p and Rgf2p through Rho1p to activate glucan synthase (GS)
  • PMID:23907979
    wsc1Ξ” and mtl2Ξ” cells showed a low level of Rho1p-GTP under cell wall stress

References

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Suggested Questions for Experts

Q: Does the phosphorylation at Ser-354 in the Wsc1 cytoplasmic tail regulate its interaction with Rgf2 or its signaling output?

Suggested experts: Yolanda Sanchez, Nicolas Minc

Q: What is the relationship between Wsc1 clustering dynamics and Rho1 activation kinetics at growing tips?

Suggested experts: Nicolas Minc, Ramakanth Neeli-Venkata

Q: Does Wsc1 have additional downstream effectors beyond the Rgf2-Rho1-glucan synthase pathway, particularly under specific stress conditions?

Suggested experts: Yolanda Sanchez, Patricia Garcia

Suggested Experiments

Experiment: FRAP and single-molecule tracking of Wsc1-GFP in rgf2-delta and rho1 temperature-sensitive mutants to determine if downstream signaling feeds back on Wsc1 clustering dynamics

Type: live-cell imaging

Experiment: Phosphomimetic (S354D) and phospho-dead (S354A) mutations in Wsc1 to test whether cytoplasmic tail phosphorylation affects Rgf2 interaction or glucan synthase activation

Type: site-directed mutagenesis and biochemistry

Experiment: Co-immunoprecipitation or proximity labeling (BioID) of Wsc1 cytoplasmic tail to identify additional interacting partners beyond Rgf2

Type: proteomics

Deep Research

Bioreason Pro

(wsc1-deep-research-bioreason-sft.md)

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Falcon

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πŸ“š Additional Documentation

Notes

(wsc1-notes.md)

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Bioreason Sft Review

(wsc1-bioreason-sft-review.md)

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